diff --git a/CHANGELOG.md b/CHANGELOG.md
index 208aa1061..6d9c6e2ea 100644
--- a/CHANGELOG.md
+++ b/CHANGELOG.md
@@ -11,6 +11,8 @@ and this project adheres to [Semantic Versioning](https://semver.org/spec/v2.0.0
 - Tests for call_repeat_expansions and qc_bam subworkflows [#713](https://github.com/nf-core/raredisease/pull/713)
 - Feature to subsample mitochondrial alignments based on number of reads [#748](https://github.com/nf-core/raredisease/pull/748)
 - Functionality to generate coverage information using Sambamba depth [#752](https://github.com/nf-core/raredisease/pull/752)
+- Added GATK contamination check for WES/WGS samples as complement to VerifyBamID2 [#758](https://github.com/nf-core/raredisease/pull/758)
+- GATK Contamination results displayed in MultiQC with color-coded thresholds [#758](https://github.com/nf-core/raredisease/pull/758)
 
 ### `Changed`
 
@@ -31,9 +33,12 @@ and this project adheres to [Semantic Versioning](https://semver.org/spec/v2.0.0
 
 ### Parameters
 
-| Old parameter | New parameter    |
-| ------------- | ---------------- |
-|               | sambamba_regions |
+| Old parameter | New parameter           |
+| ------------- | ----------------------- |
+|               | sambamba_regions        |
+|               | run_contamination       |
+|               | contamination_sites     |
+|               | contamination_sites_tbi |
 
 ### Tool updates
 
@@ -48,6 +53,8 @@ and this project adheres to [Semantic Versioning](https://semver.org/spec/v2.0.0
 | gens-preproc                        | 1.0.11      | 1.1.2       |
 | samtools (sort & view)              | 1.21        | 1.22.1      |
 | sambamba                            |             | 1.0.1       |
+| gatk4/calculatecontamination        |             | 4.6.2.0     |
+| gatk4/getpileupsummaries            |             | 4.6.2.0     |
 
 ## 2.6.0 - Cacofonix [2025-06-25]
 
diff --git a/assets/multiqc_config.yml b/assets/multiqc_config.yml
index 034fb00ed..bd604186a 100644
--- a/assets/multiqc_config.yml
+++ b/assets/multiqc_config.yml
@@ -6,7 +6,6 @@ report_comment: >
   target="_blank">nf-core/raredisease</a> analysis pipeline. For information about
   how to interpret these results, please see the <a href="https://nf-co.re/raredisease/dev/docs/output"
   target="_blank">documentation</a>.
-
 report_section_order:
   "nf-core-raredisease-methods-description":
     order: -1000
@@ -14,9 +13,9 @@ report_section_order:
     order: -1001
   "nf-core-raredisease-summary":
     order: -1002
-
+  gatk_contamination:
+    order: 1050
 export_plots: true
-
 run_modules:
   - fastqc
   - fastp
@@ -28,7 +27,6 @@ run_modules:
   - peddy
   - verifybamid
   - custom_content
-
 module_order:
   - fastqc:
       name: "FastQC"
@@ -51,8 +49,52 @@ module_order:
   - verifybamid:
       name: "VerifyBamID2"
 
+# Custom content configuration for GATK contamination
+custom_data:
+  gatk_contamination:
+    id: "gatk_contamination"
+    section_name: "GATK Contamination"
+    description: "Sample contamination estimates from GATK CalculateContamination based on common variant allele frequencies"
+    plot_type: "generalstats"
+    pconfig:
+      contamination_pct:
+        title: "Contamination"
+        description: "Estimated sample contamination percentage"
+        max: 10
+        min: 0
+        scale: "RdYlGn-rev"
+        suffix: "%"
+        format: "{:,.2f}"
+        shared_key: "contamination"
+
+# Make contamination visible in general stats by default
+table_columns_visible:
+  gatk_contamination:
+    contamination_pct: true
+
+# Color coding thresholds for contamination
+table_cond_formatting_rules:
+  contamination_pct:
+    pass:
+      - s_eq: "pass"
+      - lt: 2.0
+    warn:
+      - s_eq: "warn"
+      - lt: 5.0
+      - gte: 2.0
+    fail:
+      - s_eq: "fail"
+      - gte: 5.0
+
+# Add to General Statistics table configuration
+table_columns_placement:
+  gatk_contamination:
+    contamination_pct: 900
+
 extra_fn_clean_exts:
   - "_sorted_md"
+  - "_contamination"
+  - "_pileups"
   - type: regex
     pattern: "_LNUMBER[0-9]{1,}"
 
diff --git a/conf/modules/contamination.config b/conf/modules/contamination.config
new file mode 100644
index 000000000..f07ebeca2
--- /dev/null
+++ b/conf/modules/contamination.config
@@ -0,0 +1,46 @@
+/*
+~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
+    Config file for GATK contamination checking modules
+~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
+*/
+
+process {
+
+    //
+    // GATK GetPileupSummaries
+    //
+    withName: '.*:CONTAMINATION_CHECK:GATK4_GETPILEUPSUMMARIES' {
+        ext.args = ''
+        ext.prefix = { "${meta.id}_pileups" }
+        publishDir = [
+            path: { "${params.outdir}/qc/contamination/pileups" },
+            mode: params.publish_dir_mode,
+            saveAs: { filename -> filename.equals('versions.yml') ? null : filename }
+        ]
+    }
+
+    //
+    // GATK CalculateContamination
+    //
+    withName: '.*:CONTAMINATION_CHECK:GATK4_CALCULATECONTAMINATION' {
+        ext.args = ''
+        ext.prefix = { "${meta.id}_contamination" }
+        publishDir = [
+            path: { "${params.outdir}/qc/contamination" },
+            mode: params.publish_dir_mode,
+            saveAs: { filename -> filename.equals('versions.yml') ? null : filename }
+        ]
+    }
+
+    //
+    // Parse contamination results for MultiQC
+    //
+    withName: '.*:RAREDISEASE:PARSE_CONTAMINATION' {
+        ext.prefix = { "${meta.id}_contamination" }
+        publishDir = [
+            path: { "${params.outdir}/multiqc" },
+            mode: params.publish_dir_mode,
+            pattern: '*_mqc.tsv'
+        ]
+    }
+}
diff --git a/modules.json b/modules.json
index 56535bc9b..be7408569 100644
--- a/modules.json
+++ b/modules.json
@@ -257,6 +257,16 @@
                         "git_sha": "666652151335353eef2fcd58880bcef5bc2928e1",
                         "installed_by": ["modules"]
                     },
+                    "gatk4/calculatecontamination": {
+                        "branch": "master",
+                        "git_sha": "ae8cd884f895585c6799ab4eb6a2c9f44df03336",
+                        "installed_by": ["modules"]
+                    },
+                    "gatk4/getpileupsummaries": {
+                        "branch": "master",
+                        "git_sha": "ae8cd884f895585c6799ab4eb6a2c9f44df03336",
+                        "installed_by": ["modules"]
+                    },
                     "gawk": {
                         "branch": "master",
                         "git_sha": "5ee4d69ed992c3ce81cfbbdd0bef932fcb81c75a",
diff --git a/modules/local/parse_contamination/bin/parse_contamination.py b/modules/local/parse_contamination/bin/parse_contamination.py
new file mode 100755
index 000000000..5f5b3f1e0
--- /dev/null
+++ b/modules/local/parse_contamination/bin/parse_contamination.py
@@ -0,0 +1,40 @@
+#!/usr/bin/env python3
+"""Parse GATK CalculateContamination output for MultiQC."""
+
+import argparse
+
+
+def parse_contamination(contamination_table, sample_id, prefix):
+    """Parse contamination table and write MultiQC output."""
+    with open(contamination_table, 'r') as f:
+        lines = f.readlines()
+        data_line = lines[1].strip().split('\t')
+        contamination = float(data_line[1])
+        contamination_pct = contamination * 100
+
+    with open(f"{prefix}_contamination_mqc.tsv", 'w') as out:
+        out.write("# id: 'gatk_contamination'\n")
+        out.write("# section_name: 'GATK Contamination'\n")
+        out.write("# description: 'Sample contamination estimates from GATK CalculateContamination'\n")
+        out.write("# plot_type: 'generalstats'\n")
+        out.write("# pconfig:\n")
+        out.write("#     contamination_pct:\n")
+        out.write("#         title: 'Contamination'\n")
+        out.write("#         description: 'Estimated sample contamination percentage'\n")
+        out.write("#         max: 10\n")
+        out.write("#         min: 0\n")
+        out.write("#         scale: 'RdYlGn-rev'\n")
+        out.write("#         suffix: '%'\n")
+        out.write("#         format: '{:,.2f}'\n")
+        out.write("Sample\tcontamination_pct\n")
+        out.write(f"{sample_id}\t{contamination_pct:.4f}\n")
+
+
+if __name__ == "__main__":
+    parser = argparse.ArgumentParser(description="Parse GATK contamination output for MultiQC")
+    parser.add_argument("--input", required=True, help="GATK contamination table")
+    parser.add_argument("--sample_id", required=True, help="Sample ID")
+    parser.add_argument("--prefix", required=True, help="Output prefix")
+    args = parser.parse_args()
+
+    parse_contamination(args.input, args.sample_id, args.prefix)
diff --git a/modules/local/parse_contamination/environment.yml b/modules/local/parse_contamination/environment.yml
new file mode 100644
index 000000000..b5260d32d
--- /dev/null
+++ b/modules/local/parse_contamination/environment.yml
@@ -0,0 +1,7 @@
+name: parse_contamination
+channels:
+  - conda-forge
+  - bioconda
+  - defaults
+dependencies:
+  - python=3.11
diff --git a/modules/local/parse_contamination/main.nf b/modules/local/parse_contamination/main.nf
new file mode 100644
index 000000000..d8be68d13
--- /dev/null
+++ b/modules/local/parse_contamination/main.nf
@@ -0,0 +1,44 @@
+process PARSE_CONTAMINATION {
+    tag "$meta.id"
+    label 'process_single'
+
+    conda "${moduleDir}/environment.yml"
+    container "${ workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container ?
+        'https://depot.galaxyproject.org/singularity/python:3.11' :
+        'biocontainers/python:3.11' }"
+
+    input:
+    tuple val(meta), path(contamination_table)
+
+    output:
+    tuple val(meta), path("*_contamination_mqc.tsv"), emit: mqc_table
+    path "versions.yml"                             , emit: versions
+
+    when:
+    task.ext.when == null || task.ext.when
+
+    script:
+    def prefix = task.ext.prefix ?: "${meta.id}"
+    """
+    python3 ${moduleDir}/bin/parse_contamination.py \\
+        --input ${contamination_table} \\
+        --sample_id ${meta.id} \\
+        --prefix ${prefix}
+
+    cat <<-END_VERSIONS > versions.yml
+    "${task.process}":
+        python: \$(python --version | sed 's/Python //')
+    END_VERSIONS
+    """
+
+    stub:
+    def prefix = task.ext.prefix ?: "${meta.id}"
+    """
+    touch ${prefix}_contamination_mqc.tsv
+
+    cat <<-END_VERSIONS > versions.yml
+    "${task.process}":
+        python: \$(python --version | sed 's/Python //')
+    END_VERSIONS
+    """
+}
diff --git a/modules/local/parse_contamination/meta.yml b/modules/local/parse_contamination/meta.yml
new file mode 100644
index 000000000..6018fd2df
--- /dev/null
+++ b/modules/local/parse_contamination/meta.yml
@@ -0,0 +1,29 @@
+name: parse_contamination
+description: Parse GATK CalculateContamination output for MultiQC
+keywords:
+  - contamination
+  - MultiQC
+  - parsing
+tools:
+  - python:
+      description: Python programming language
+      homepage: https://www.python.org/
+input:
+  - meta:
+      type: map
+      description: Groovy Map containing sample information
+  - contamination_table:
+      type: file
+      description: GATK CalculateContamination output table
+      pattern: "*.contamination.table"
+output:
+  - mqc_table:
+      type: file
+      description: MultiQC custom content table
+      pattern: "*_contamination_mqc.tsv"
+  - versions:
+      type: file
+      description: File containing software versions
+      pattern: "versions.yml"
+authors:
+  - "56053vujinovic"
diff --git a/modules/nf-core/gatk4/calculatecontamination/environment.yml b/modules/nf-core/gatk4/calculatecontamination/environment.yml
new file mode 100644
index 000000000..67e0eb860
--- /dev/null
+++ b/modules/nf-core/gatk4/calculatecontamination/environment.yml
@@ -0,0 +1,10 @@
+---
+# yaml-language-server: $schema=https://raw.githubusercontent.com/nf-core/modules/master/modules/environment-schema.json
+channels:
+  - conda-forge
+  - bioconda
+dependencies:
+  # renovate: datasource=conda depName=bioconda/gatk4
+  - bioconda::gatk4=4.6.2.0
+  # renovate: datasource=conda depName=bioconda/gcnvkernel
+  - bioconda::gcnvkernel=0.9
diff --git a/modules/nf-core/gatk4/calculatecontamination/main.nf b/modules/nf-core/gatk4/calculatecontamination/main.nf
new file mode 100644
index 000000000..0b8706e76
--- /dev/null
+++ b/modules/nf-core/gatk4/calculatecontamination/main.nf
@@ -0,0 +1,59 @@
+process GATK4_CALCULATECONTAMINATION {
+    tag "${meta.id}"
+    label 'process_low'
+
+    conda "${moduleDir}/environment.yml"
+    container "${workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container
+        ? 'https://community-cr-prod.seqera.io/docker/registry/v2/blobs/sha256/ce/ced519873646379e287bc28738bdf88e975edd39a92e7bc6a34bccd37153d9d0/data'
+        : 'community.wave.seqera.io/library/gatk4_gcnvkernel:edb12e4f0bf02cd3'}"
+
+    input:
+    tuple val(meta), path(pileup), path(matched)
+
+    output:
+    tuple val(meta), path('*.contamination.table'), emit: contamination
+    tuple val(meta), path('*.segmentation.table'),  emit: segmentation, optional: true
+    path "versions.yml",                            emit: versions
+
+    when:
+    task.ext.when == null || task.ext.when
+
+    script:
+    def args = task.ext.args ?: ''
+    def prefix = task.ext.prefix ?: "${meta.id}"
+    def matched_command = matched ? "--matched-normal ${matched}" : ''
+
+    def avail_mem = 3072
+    if (!task.memory) {
+        log.info('[GATK CalculateContamination] Available memory not known - defaulting to 3GB. Specify process memory requirements to change this.')
+    }
+    else {
+        avail_mem = (task.memory.mega * 0.8).intValue()
+    }
+    """
+    gatk --java-options "-Xmx${avail_mem}M -XX:-UsePerfData" \\
+        CalculateContamination \\
+        --input ${pileup} \\
+        --output ${prefix}.contamination.table \\
+        ${matched_command} \\
+        --tmp-dir . \\
+        ${args}
+
+    cat <<-END_VERSIONS > versions.yml
+    "${task.process}":
+        gatk4: \$(echo \$(gatk --version 2>&1) | sed 's/^.*(GATK) v//; s/ .*\$//')
+    END_VERSIONS
+    """
+
+    stub:
+    prefix = task.ext.prefix ?: "${meta.id}"
+    """
+    touch ${prefix}.contamination.table
+    touch ${prefix}.segmentation.table
+
+    cat <<-END_VERSIONS > versions.yml
+    "${task.process}":
+        gatk4: \$(echo \$(gatk --version 2>&1) | sed 's/^.*(GATK) v//; s/ .*\$//')
+    END_VERSIONS
+    """
+}
diff --git a/modules/nf-core/gatk4/calculatecontamination/meta.yml b/modules/nf-core/gatk4/calculatecontamination/meta.yml
new file mode 100644
index 000000000..477e9d3b1
--- /dev/null
+++ b/modules/nf-core/gatk4/calculatecontamination/meta.yml
@@ -0,0 +1,76 @@
+name: gatk4_calculatecontamination
+description: |
+  Calculates the fraction of reads from cross-sample contamination based on summary tables from getpileupsummaries. Output to be used with filtermutectcalls.
+keywords:
+  - gatk4
+  - calculatecontamination
+  - cross-samplecontamination
+  - getpileupsummaries
+  - filtermutectcalls
+tools:
+  - gatk4:
+      description: |
+        Developed in the Data Sciences Platform at the Broad Institute, the toolkit offers a wide variety of tools
+        with a primary focus on variant discovery and genotyping. Its powerful processing engine
+        and high-performance computing features make it capable of taking on projects of any size.
+      homepage: https://gatk.broadinstitute.org/hc/en-us
+      documentation: https://gatk.broadinstitute.org/hc/en-us/categories/360002369672s
+      doi: 10.1158/1538-7445.AM2017-3590
+      licence: ["Apache-2.0"]
+      identifier: ""
+input:
+  - - meta:
+        type: map
+        description: |
+          Groovy Map containing sample information
+          e.g. [ id:'test' ]
+    - pileup:
+        type: file
+        description: File containing the pileups summary table of a tumor sample to
+          be used to calculate contamination.
+        pattern: "*.pileups.table"
+        ontologies: []
+    - matched:
+        type: file
+        description: File containing the pileups summary table of a normal sample that
+          matches with the tumor sample specified in pileup argument. This is an optional
+          input.
+        pattern: "*.pileups.table"
+        ontologies: []
+output:
+  contamination:
+    - - meta:
+          type: file
+          description: File containing the contamination table.
+          pattern: "*.contamination.table"
+          ontologies: []
+      - "*.contamination.table":
+          type: file
+          description: File containing the contamination table.
+          pattern: "*.contamination.table"
+          ontologies: []
+  segmentation:
+    - - meta:
+          type: file
+          description: File containing the contamination table.
+          pattern: "*.contamination.table"
+          ontologies: []
+      - "*.segmentation.table":
+          type: file
+          description: output table containing segmentation of tumor minor allele fractions
+            (optional)
+          pattern: "*.segmentation.table"
+          ontologies: []
+  versions:
+    - versions.yml:
+        type: file
+        description: File containing software versions
+        pattern: "versions.yml"
+        ontologies:
+          - edam: http://edamontology.org/format_3750 # YAML
+authors:
+  - "@GCJMackenzie"
+  - "@maxulysse"
+maintainers:
+  - "@GCJMackenzie"
+  - "@maxulysse"
diff --git a/modules/nf-core/gatk4/calculatecontamination/tests/main.nf.test b/modules/nf-core/gatk4/calculatecontamination/tests/main.nf.test
new file mode 100644
index 000000000..81f048f67
--- /dev/null
+++ b/modules/nf-core/gatk4/calculatecontamination/tests/main.nf.test
@@ -0,0 +1,106 @@
+nextflow_process {
+
+    name "Test Process GATK4_CALCULATECONTAMINATION"
+    script "../main.nf"
+    process "GATK4_CALCULATECONTAMINATION"
+
+    tag "modules"
+    tag "modules_nfcore"
+    tag "gatk4"
+    tag "gatk4/calculatecontamination"
+
+    test("human - pileup-table") {
+
+        when {
+            process {
+                """
+                input[0] = [ [ id:'test' ], // meta map
+                    file(params.modules_testdata_base_path + 'genomics/homo_sapiens/illumina/gatk/test2.pileups.table', checkIfExists: true),
+                    [] ]
+                """
+            }
+        }
+
+        then {
+            assertAll(
+                { assert process.success },
+                { assert snapshot(process.out.versions).match("versions") },
+                { assert snapshot(file(process.out.contamination.get(0).get(1)).readLines()[0]).match() }
+            )
+        }
+
+    }
+
+    test("human - pileup-table - matched-pair") {
+
+        when {
+            process {
+                """
+                input[0] = [ [ id:'test' ], // meta map
+                    file(params.modules_testdata_base_path + 'genomics/homo_sapiens/illumina/gatk/test2.pileups.table', checkIfExists: true),
+                    file(params.modules_testdata_base_path + 'genomics/homo_sapiens/illumina/gatk/test.pileups.table', checkIfExists: true)
+                    ]
+                """
+            }
+        }
+
+        then {
+            assertAll(
+                { assert process.success },
+                { assert snapshot(process.out.versions).match("versions_pair") },
+                { assert snapshot(file(process.out.contamination.get(0).get(1)).readLines()[0]).match() }
+            )
+        }
+
+    }
+
+    test("human - pileup-table - segmentation") {
+
+        config "./nextflow.config"
+
+        when {
+            process {
+                """
+                input[0] = [ [ id:'test' ], // meta map
+                    file(params.modules_testdata_base_path + 'genomics/homo_sapiens/illumina/gatk/test2.pileups.table', checkIfExists: true),
+                    file(params.modules_testdata_base_path + 'genomics/homo_sapiens/illumina/gatk/test.pileups.table', checkIfExists: true)
+                    ]
+                """
+            }
+        }
+
+        then {
+            assertAll(
+                { assert process.success },
+                { assert snapshot(process.out.versions).match("versions_segmentation") },
+                { assert snapshot(file(process.out.contamination.get(0).get(1)).readLines()[0]).match("contamination") },
+                { assert snapshot(file(process.out.segmentation.get(0).get(1)).readLines()[0]).match("segmentation") }
+            )
+        }
+
+    }
+
+    test("human - pileup-table - stub") {
+
+        options "-stub"
+
+        when {
+            process {
+                """
+                input[0] = [ [ id:'test' ], // meta map
+                    file(params.modules_testdata_base_path + 'genomics/homo_sapiens/illumina/gatk/test2.pileups.table', checkIfExists: true),
+                    [] ]
+                """
+            }
+        }
+
+        then {
+            assertAll(
+                { assert process.success },
+                { assert snapshot(process.out).match() }
+            )
+        }
+
+    }
+
+}
diff --git a/modules/nf-core/gatk4/calculatecontamination/tests/main.nf.test.snap b/modules/nf-core/gatk4/calculatecontamination/tests/main.nf.test.snap
new file mode 100644
index 000000000..4ef184bfc
--- /dev/null
+++ b/modules/nf-core/gatk4/calculatecontamination/tests/main.nf.test.snap
@@ -0,0 +1,127 @@
+{
+    "versions_pair": {
+        "content": [
+            [
+                "versions.yml:md5,703ef3c3104ffcb977090771a8761da2"
+            ]
+        ],
+        "meta": {
+            "nf-test": "0.9.2",
+            "nextflow": "25.04.7"
+        },
+        "timestamp": "2025-09-15T12:29:33.077296321"
+    },
+    "versions": {
+        "content": [
+            [
+                "versions.yml:md5,703ef3c3104ffcb977090771a8761da2"
+            ]
+        ],
+        "meta": {
+            "nf-test": "0.9.2",
+            "nextflow": "25.04.7"
+        },
+        "timestamp": "2025-09-15T12:29:20.224234796"
+    },
+    "versions_segmentation": {
+        "content": [
+            [
+                "versions.yml:md5,703ef3c3104ffcb977090771a8761da2"
+            ]
+        ],
+        "meta": {
+            "nf-test": "0.9.2",
+            "nextflow": "25.04.7"
+        },
+        "timestamp": "2025-09-15T12:29:45.806413439"
+    },
+    "segmentation": {
+        "content": [
+            "#<METADATA>SAMPLE=tumour"
+        ],
+        "meta": {
+            "nf-test": "0.8.4",
+            "nextflow": "23.10.0"
+        },
+        "timestamp": "2024-05-15T12:57:38.845287"
+    },
+    "human - pileup-table": {
+        "content": [
+            "sample\tcontamination\terror"
+        ],
+        "meta": {
+            "nf-test": "0.8.4",
+            "nextflow": "23.10.0"
+        },
+        "timestamp": "2024-05-15T11:09:16.292509"
+    },
+    "human - pileup-table - stub": {
+        "content": [
+            {
+                "0": [
+                    [
+                        {
+                            "id": "test"
+                        },
+                        "test.contamination.table:md5,d41d8cd98f00b204e9800998ecf8427e"
+                    ]
+                ],
+                "1": [
+                    [
+                        {
+                            "id": "test"
+                        },
+                        "test.segmentation.table:md5,d41d8cd98f00b204e9800998ecf8427e"
+                    ]
+                ],
+                "2": [
+                    "versions.yml:md5,703ef3c3104ffcb977090771a8761da2"
+                ],
+                "contamination": [
+                    [
+                        {
+                            "id": "test"
+                        },
+                        "test.contamination.table:md5,d41d8cd98f00b204e9800998ecf8427e"
+                    ]
+                ],
+                "segmentation": [
+                    [
+                        {
+                            "id": "test"
+                        },
+                        "test.segmentation.table:md5,d41d8cd98f00b204e9800998ecf8427e"
+                    ]
+                ],
+                "versions": [
+                    "versions.yml:md5,703ef3c3104ffcb977090771a8761da2"
+                ]
+            }
+        ],
+        "meta": {
+            "nf-test": "0.9.2",
+            "nextflow": "25.04.7"
+        },
+        "timestamp": "2025-09-15T12:29:55.994434812"
+    },
+    "human - pileup-table - matched-pair": {
+        "content": [
+            "sample\tcontamination\terror"
+        ],
+        "meta": {
+            "nf-test": "0.8.4",
+            "nextflow": "23.10.0"
+        },
+        "timestamp": "2024-05-15T11:09:26.408848"
+    },
+    "contamination": {
+        "content": [
+            "sample\tcontamination\terror"
+        ],
+        "meta": {
+            "nf-test": "0.8.4",
+            "nextflow": "23.10.0"
+        },
+        "timestamp": "2024-05-15T12:57:38.840651"
+    }
+}
\ No newline at end of file
diff --git a/modules/nf-core/gatk4/calculatecontamination/tests/nextflow.config b/modules/nf-core/gatk4/calculatecontamination/tests/nextflow.config
new file mode 100644
index 000000000..db836b7f8
--- /dev/null
+++ b/modules/nf-core/gatk4/calculatecontamination/tests/nextflow.config
@@ -0,0 +1,5 @@
+process {
+    withName: GATK4_CALCULATECONTAMINATION {
+        ext.args = { "--tumor-segmentation ${meta.id}.segmentation.table" }
+    }
+}
diff --git a/modules/nf-core/gatk4/getpileupsummaries/environment.yml b/modules/nf-core/gatk4/getpileupsummaries/environment.yml
new file mode 100644
index 000000000..67e0eb860
--- /dev/null
+++ b/modules/nf-core/gatk4/getpileupsummaries/environment.yml
@@ -0,0 +1,10 @@
+---
+# yaml-language-server: $schema=https://raw.githubusercontent.com/nf-core/modules/master/modules/environment-schema.json
+channels:
+  - conda-forge
+  - bioconda
+dependencies:
+  # renovate: datasource=conda depName=bioconda/gatk4
+  - bioconda::gatk4=4.6.2.0
+  # renovate: datasource=conda depName=bioconda/gcnvkernel
+  - bioconda::gcnvkernel=0.9
diff --git a/modules/nf-core/gatk4/getpileupsummaries/main.nf b/modules/nf-core/gatk4/getpileupsummaries/main.nf
new file mode 100644
index 000000000..d0cabdaf8
--- /dev/null
+++ b/modules/nf-core/gatk4/getpileupsummaries/main.nf
@@ -0,0 +1,65 @@
+process GATK4_GETPILEUPSUMMARIES {
+    tag "${meta.id}"
+    label 'process_low'
+
+    conda "${moduleDir}/environment.yml"
+    container "${workflow.containerEngine == 'singularity' && !task.ext.singularity_pull_docker_container
+        ? 'https://community-cr-prod.seqera.io/docker/registry/v2/blobs/sha256/ce/ced519873646379e287bc28738bdf88e975edd39a92e7bc6a34bccd37153d9d0/data'
+        : 'community.wave.seqera.io/library/gatk4_gcnvkernel:edb12e4f0bf02cd3'}"
+
+    input:
+    tuple val(meta), path(input), path(index), path(intervals)
+    tuple val(meta2), path(fasta)
+    tuple val(meta3), path(fai)
+    tuple val(meta4), path(dict)
+    path variants
+    path variants_tbi
+
+    output:
+    tuple val(meta), path('*.pileups.table'), emit: table
+    path "versions.yml",                      emit: versions
+
+    when:
+    task.ext.when == null || task.ext.when
+
+    script:
+    def args = task.ext.args ?: ''
+    def prefix = task.ext.prefix ?: "${meta.id}"
+    def interval_command = intervals ? "--intervals ${intervals}" : "--intervals ${variants}"
+    def reference_command = fasta ? "--reference ${fasta}" : ''
+
+    def avail_mem = 3072
+    if (!task.memory) {
+        log.info('[GATK GetPileupSummaries] Available memory not known - defaulting to 3GB. Specify process memory requirements to change this.')
+    }
+    else {
+        avail_mem = (task.memory.mega * 0.8).intValue()
+    }
+    """
+    gatk --java-options "-Xmx${avail_mem}M -XX:-UsePerfData" \\
+        GetPileupSummaries \\
+        --input ${input} \\
+        --variant ${variants} \\
+        --output ${prefix}.pileups.table \\
+        ${reference_command} \\
+        ${interval_command} \\
+        --tmp-dir . \\
+        ${args}
+
+    cat <<-END_VERSIONS > versions.yml
+    "${task.process}":
+        gatk4: \$(echo \$(gatk --version 2>&1) | sed 's/^.*(GATK) v//; s/ .*\$//')
+    END_VERSIONS
+    """
+
+    stub:
+    def prefix = task.ext.prefix ?: "${meta.id}"
+    """
+    touch ${prefix}.pileups.table
+
+    cat <<-END_VERSIONS > versions.yml
+    "${task.process}":
+        gatk4: \$(echo \$(gatk --version 2>&1) | sed 's/^.*(GATK) v//; s/ .*\$//')
+    END_VERSIONS
+    """
+}
diff --git a/modules/nf-core/gatk4/getpileupsummaries/meta.yml b/modules/nf-core/gatk4/getpileupsummaries/meta.yml
new file mode 100644
index 000000000..d7f66ad19
--- /dev/null
+++ b/modules/nf-core/gatk4/getpileupsummaries/meta.yml
@@ -0,0 +1,106 @@
+name: gatk4_getpileupsummaries
+description: |
+  Summarizes counts of reads that support reference, alternate and other alleles for given sites. Results can be used with CalculateContamination. Requires a common germline variant sites file, such as from gnomAD.
+keywords:
+  - gatk4
+  - germlinevariantsites
+  - getpileupsumaries
+  - readcountssummary
+tools:
+  - gatk4:
+      description: |
+        Developed in the Data Sciences Platform at the Broad Institute, the toolkit offers a wide variety of tools
+        with a primary focus on variant discovery and genotyping. Its powerful processing engine
+        and high-performance computing features make it capable of taking on projects of any size.
+      homepage: https://gatk.broadinstitute.org/hc/en-us
+      documentation: https://gatk.broadinstitute.org/hc/en-us/categories/360002369672s
+      doi: 10.1158/1538-7445.AM2017-3590
+      licence: ["Apache-2.0"]
+      identifier: ""
+input:
+  - - meta:
+        type: map
+        description: |
+          Groovy Map containing sample information
+          e.g. [ id:'test' ]
+    - input:
+        type: file
+        description: BAM/CRAM file to be summarised.
+        pattern: "*.{bam,cram}"
+        ontologies: []
+    - index:
+        type: file
+        description: Index file for the input BAM/CRAM file.
+        pattern: "*.{bam.bai,cram.crai}"
+        ontologies: []
+    - intervals:
+        type: file
+        description: File containing specified sites to be used for the summary. If
+          this option is not specified, variants file is used instead automatically.
+        pattern: "*.interval_list"
+        ontologies: []
+  - - meta2:
+        type: map
+        description: |
+          Groovy Map containing reference information
+          e.g. [ id:'genome' ]
+    - fasta:
+        type: file
+        description: The reference fasta file
+        pattern: "*.fasta"
+        ontologies: []
+  - - meta3:
+        type: map
+        description: |
+          Groovy Map containing reference information
+          e.g. [ id:'genome' ]
+    - fai:
+        type: file
+        description: Index of reference fasta file
+        pattern: "*.fasta.fai"
+        ontologies: []
+  - - meta4:
+        type: map
+        description: |
+          Groovy Map containing reference information
+          e.g. [ id:'genome' ]
+    - dict:
+        type: file
+        description: GATK sequence dictionary
+        pattern: "*.dict"
+        ontologies: []
+  - variants:
+      type: file
+      description: Population vcf of germline sequencing, containing allele fractions.
+        Is also used as sites file if no separate sites file is specified.
+      pattern: "*.vcf.gz"
+      ontologies:
+        - edam: http://edamontology.org/format_3989 # GZIP format
+  - variants_tbi:
+      type: file
+      description: Index file for the germline resource.
+      pattern: "*.vcf.gz.tbi"
+      ontologies: []
+output:
+  table:
+    - - meta:
+          type: map
+          description: |
+            Groovy Map containing sample information
+            e.g. [ id:'test' ]
+      - "*.pileups.table":
+          type: file
+          description: Table containing read counts for each site.
+          pattern: "*.pileups.table"
+          ontologies: []
+  versions:
+    - versions.yml:
+        type: file
+        description: File containing software versions
+        pattern: "versions.yml"
+        ontologies:
+          - edam: http://edamontology.org/format_3750 # YAML
+authors:
+  - "@GCJMackenzie"
+maintainers:
+  - "@GCJMackenzie"
diff --git a/modules/nf-core/gatk4/getpileupsummaries/tests/main.nf.test b/modules/nf-core/gatk4/getpileupsummaries/tests/main.nf.test
new file mode 100644
index 000000000..79cd6344c
--- /dev/null
+++ b/modules/nf-core/gatk4/getpileupsummaries/tests/main.nf.test
@@ -0,0 +1,104 @@
+nextflow_process {
+
+    name "Test Process GATK4_GETPILEUPSUMMARIES"
+    script "../main.nf"
+    process "GATK4_GETPILEUPSUMMARIES"
+
+    tag "modules"
+    tag "modules_nfcore"
+    tag "gatk4"
+    tag "gatk4/getpileupsummaries"
+
+    test("human - bam") {
+
+        when {
+            process {
+                """
+                input[0] = [ [ id:'test' ], // meta map
+                    file(params.modules_testdata_base_path + 'genomics/homo_sapiens/illumina/bam/test.paired_end.recalibrated.sorted.bam', checkIfExists: true) ,
+                    file(params.modules_testdata_base_path + 'genomics/homo_sapiens/illumina/bam/test.paired_end.recalibrated.sorted.bam.bai', checkIfExists: true),
+                    file(params.modules_testdata_base_path + 'genomics/homo_sapiens/genome/chr21/sequence/genome.interval_list', checkIfExists: true)
+                ]
+                input[1] = [[],[]] // fasta
+                input[2] = [[],[]] // fai
+                input[3] = [[],[]] // dict
+                input[4] = file(params.modules_testdata_base_path + 'genomics/homo_sapiens/genome/chr21/germlineresources/gnomAD.r2.1.1.vcf.gz', checkIfExists: true)
+                input[5] = file(params.modules_testdata_base_path + 'genomics/homo_sapiens/genome/chr21/germlineresources/gnomAD.r2.1.1.vcf.gz.tbi', checkIfExists: true)
+                """
+            }
+        }
+
+        then {
+            assertAll(
+                { assert process.success },
+                { assert snapshot(process.out).match() }
+            )
+        }
+
+    }
+
+    test("human - cram") {
+
+        when {
+            process {
+                """
+                input[0] = [ [ id:'test' ], // meta map
+                    file(params.modules_testdata_base_path + 'genomics/homo_sapiens/illumina/cram/test.paired_end.recalibrated.sorted.cram', checkIfExists: true) ,
+                    file(params.modules_testdata_base_path + 'genomics/homo_sapiens/illumina/cram/test.paired_end.recalibrated.sorted.cram.crai', checkIfExists: true),
+                    file(params.modules_testdata_base_path + 'genomics/homo_sapiens/genome/chr21/sequence/genome.interval_list', checkIfExists: true)
+                    ]
+                input[1] = [ [ id:'genome' ], // meta map
+                        file(params.modules_testdata_base_path + 'genomics/homo_sapiens/genome/chr21/sequence/genome.fasta', checkIfExists: true)
+                    ]
+                input[2] = [ [ id:'genome' ], // meta map
+                        file(params.modules_testdata_base_path + 'genomics/homo_sapiens/genome/chr21/sequence/genome.fasta.fai', checkIfExists: true)
+                    ]
+                input[3] = [ [ id:'genome' ], // meta map
+                        file(params.modules_testdata_base_path + 'genomics/homo_sapiens/genome/chr21/sequence/genome.dict', checkIfExists: true)
+                    ]
+                input[4] = file(params.modules_testdata_base_path + 'genomics/homo_sapiens/genome/chr21/germlineresources/gnomAD.r2.1.1.vcf.gz', checkIfExists: true)
+                input[5] = file(params.modules_testdata_base_path + 'genomics/homo_sapiens/genome/chr21/germlineresources/gnomAD.r2.1.1.vcf.gz.tbi', checkIfExists: true)
+                """
+            }
+        }
+
+        then {
+            assertAll(
+                { assert process.success },
+                { assert snapshot(process.out).match() }
+            )
+        }
+
+    }
+
+    test("human - bam - stub") {
+
+        options "-stub"
+
+        when {
+            process {
+                """
+                input[0] = [ [ id:'test' ], // meta map
+                    file(params.modules_testdata_base_path + 'genomics/homo_sapiens/illumina/bam/test.paired_end.recalibrated.sorted.bam', checkIfExists: true) ,
+                    file(params.modules_testdata_base_path + 'genomics/homo_sapiens/illumina/bam/test.paired_end.recalibrated.sorted.bam.bai', checkIfExists: true),
+                    file(params.modules_testdata_base_path + 'genomics/homo_sapiens/genome/chr21/sequence/genome.interval_list', checkIfExists: true)
+                ]
+                input[1] = [[],[]] // fasta
+                input[2] = [[],[]] // fai
+                input[3] = [[],[]] // dict
+                input[4] = file(params.modules_testdata_base_path + 'genomics/homo_sapiens/genome/chr21/germlineresources/gnomAD.r2.1.1.vcf.gz', checkIfExists: true)
+                input[5] = file(params.modules_testdata_base_path + 'genomics/homo_sapiens/genome/chr21/germlineresources/gnomAD.r2.1.1.vcf.gz.tbi', checkIfExists: true)
+                """
+            }
+        }
+
+        then {
+            assertAll(
+                { assert process.success },
+                { assert snapshot(process.out).match() }
+            )
+        }
+
+    }
+
+}
diff --git a/modules/nf-core/gatk4/getpileupsummaries/tests/main.nf.test.snap b/modules/nf-core/gatk4/getpileupsummaries/tests/main.nf.test.snap
new file mode 100644
index 000000000..fe713315a
--- /dev/null
+++ b/modules/nf-core/gatk4/getpileupsummaries/tests/main.nf.test.snap
@@ -0,0 +1,101 @@
+{
+    "human - bam - stub": {
+        "content": [
+            {
+                "0": [
+                    [
+                        {
+                            "id": "test"
+                        },
+                        "test.pileups.table:md5,d41d8cd98f00b204e9800998ecf8427e"
+                    ]
+                ],
+                "1": [
+                    "versions.yml:md5,e06a2d6fcf646da962971eab2035b3ee"
+                ],
+                "table": [
+                    [
+                        {
+                            "id": "test"
+                        },
+                        "test.pileups.table:md5,d41d8cd98f00b204e9800998ecf8427e"
+                    ]
+                ],
+                "versions": [
+                    "versions.yml:md5,e06a2d6fcf646da962971eab2035b3ee"
+                ]
+            }
+        ],
+        "meta": {
+            "nf-test": "0.9.2",
+            "nextflow": "25.04.7"
+        },
+        "timestamp": "2025-09-15T15:15:36.702715205"
+    },
+    "human - bam": {
+        "content": [
+            {
+                "0": [
+                    [
+                        {
+                            "id": "test"
+                        },
+                        "test.pileups.table:md5,2d7ce4a54df6b9249e12d60737a67dac"
+                    ]
+                ],
+                "1": [
+                    "versions.yml:md5,e06a2d6fcf646da962971eab2035b3ee"
+                ],
+                "table": [
+                    [
+                        {
+                            "id": "test"
+                        },
+                        "test.pileups.table:md5,2d7ce4a54df6b9249e12d60737a67dac"
+                    ]
+                ],
+                "versions": [
+                    "versions.yml:md5,e06a2d6fcf646da962971eab2035b3ee"
+                ]
+            }
+        ],
+        "meta": {
+            "nf-test": "0.9.2",
+            "nextflow": "25.04.7"
+        },
+        "timestamp": "2025-09-15T15:14:59.43518059"
+    },
+    "human - cram": {
+        "content": [
+            {
+                "0": [
+                    [
+                        {
+                            "id": "test"
+                        },
+                        "test.pileups.table:md5,2d7ce4a54df6b9249e12d60737a67dac"
+                    ]
+                ],
+                "1": [
+                    "versions.yml:md5,e06a2d6fcf646da962971eab2035b3ee"
+                ],
+                "table": [
+                    [
+                        {
+                            "id": "test"
+                        },
+                        "test.pileups.table:md5,2d7ce4a54df6b9249e12d60737a67dac"
+                    ]
+                ],
+                "versions": [
+                    "versions.yml:md5,e06a2d6fcf646da962971eab2035b3ee"
+                ]
+            }
+        ],
+        "meta": {
+            "nf-test": "0.9.2",
+            "nextflow": "25.04.7"
+        },
+        "timestamp": "2025-09-15T15:15:25.628760353"
+    }
+}
\ No newline at end of file
diff --git a/modules/nf-core/svdb/merge/main.nf b/modules/nf-core/svdb/merge/main.nf
index 104f5ad79..75b1373b6 100644
--- a/modules/nf-core/svdb/merge/main.nf
+++ b/modules/nf-core/svdb/merge/main.nf
@@ -102,4 +102,4 @@ process SVDB_MERGE {
         bcftools: \$(bcftools --version 2>&1 | head -n1 | sed 's/^.*bcftools //; s/ .*\$//')
     END_VERSIONS
     """
-}
+}
\ No newline at end of file
diff --git a/nextflow.config b/nextflow.config
index 159a6cbd3..0b59d3b00 100644
--- a/nextflow.config
+++ b/nextflow.config
@@ -32,6 +32,7 @@ params {
     run_mt_for_wes             = false
     run_rtgvcfeval             = false
     save_mapped_as_cram        = false
+    run_contamination          = false
     scatter_count              = 20
     skip_tools                 = null
     skip_subworkflows          = null
@@ -91,6 +92,8 @@ params {
     vcfanno_lua                     = null
     vep_cache                       = null
     vep_plugin_files                = null
+    contamination_sites             = null
+    contamination_sites_tbi         = null
     modules_testdata_base_path      = 'https://raw.githubusercontent.com/nf-core/test-datasets/modules/data/'
     pipelines_testdata_base_path    = 'https://raw.githubusercontent.com/nf-core/test-datasets/refs/heads/raredisease'
 
@@ -486,6 +489,8 @@ includeConfig 'conf/modules/variant_evaluation.config'
 includeConfig 'conf/modules/subsample_mt_frac.config'
 includeConfig 'conf/modules/subsample_mt_reads.config'
 includeConfig 'conf/modules/annotate_rhocallviz.config'
+includeConfig 'conf/modules/contamination.config'
+
 
 // Nextflow plugins
 plugins {
diff --git a/nextflow_schema.json b/nextflow_schema.json
index 357b122e6..8ee70783b 100644
--- a/nextflow_schema.json
+++ b/nextflow_schema.json
@@ -443,6 +443,30 @@
                     "description": "Path to UD matrix file from SVD result of genotype matrix. Used by verifybamid2.",
                     "fa_icon": "fas fa-file-csv"
                 },
+                "run_contamination": {
+                    "type": "boolean",
+                    "default": false,
+                    "description": "Run GATK contamination check in addition to VerifyBamID2.",
+                    "help_text": "GATK contamination check works better for WES samples and provides validation for WGS.",
+                    "fa_icon": "fas fa-toggle-on"
+                },
+                "contamination_sites": {
+                    "type": "string",
+                    "exists": true,
+                    "format": "file-path",
+                    "pattern": "^\\S+\\.vcf(\\.gz)?$",
+                    "description": "Path to VCF file with common variants for GATK contamination detection.",
+                    "help_text": "Use small_exac_common_3.hg38.vcf.gz for no_alt reference genomes. This file should contain common SNP sites with population allele frequencies.",
+                    "fa_icon": "fas fa-file"
+                },
+                "contamination_sites_tbi": {
+                    "type": "string",
+                    "exists": true,
+                    "format": "file-path",
+                    "pattern": "^\\S+\\.vcf(\\.gz)?\\.tbi$",
+                    "description": "Index file for contamination sites VCF.",
+                    "fa_icon": "fas fa-file"
+                },
                 "vcf2cytosure_blacklist": {
                     "type": "string",
                     "exists": true,
diff --git a/subworkflows/local/contamination_check/main.nf b/subworkflows/local/contamination_check/main.nf
new file mode 100644
index 000000000..e9ef9c757
--- /dev/null
+++ b/subworkflows/local/contamination_check/main.nf
@@ -0,0 +1,67 @@
+//
+// Subworkflow: Check sample contamination using GATK
+//
+
+include { GATK4_GETPILEUPSUMMARIES     } from '../../../modules/nf-core/gatk4/getpileupsummaries/main'
+include { GATK4_CALCULATECONTAMINATION } from '../../../modules/nf-core/gatk4/calculatecontamination/main'
+
+workflow CONTAMINATION_CHECK {
+
+    take:
+    ch_bam               // channel: [ val(meta), path(bam), path(bai) ]
+    ch_fasta             // channel: [ val(meta), path(fasta) ]
+    ch_fai               // channel: [ val(meta), path(fai) ]
+    ch_dict              // channel: [ val(meta), path(dict) ]
+    ch_contamination_vcf // channel: [ path(vcf), path(tbi) ]
+    ch_intervals         // channel: [ path(bed) ] - only used for WES, empty for WGS
+
+    main:
+    ch_versions = Channel.empty()
+
+    // Prepare BAM with intervals - conditionally based on analysis type
+    // For WGS: intervals will be empty [], for WES: intervals will contain the BED file
+    ch_bam_with_intervals = ch_bam
+        .combine(ch_intervals.ifEmpty([[]]))
+        .map { meta, bam, bai, bed ->
+            // If bed is an empty list, pass empty list; otherwise pass bed file
+            def intervals = (bed instanceof List && bed.isEmpty()) ? [] : (bed ?: [])
+            [ meta, bam, bai, intervals ]
+        }
+
+    // Separate VCF and TBI - collect them to make value channels
+    ch_variants_vcf = ch_contamination_vcf
+        .map { vcf, tbi -> vcf }
+        .collect()
+
+    ch_variants_tbi = ch_contamination_vcf
+        .map { vcf, tbi -> tbi }
+        .collect()
+
+    // Run GetPileupSummaries
+    GATK4_GETPILEUPSUMMARIES (
+        ch_bam_with_intervals,  // [meta, bam, bai, intervals]
+        ch_fasta,               // [meta2, fasta]
+        ch_fai,                 // [meta3, fai]
+        ch_dict,                // [meta4, dict]
+        ch_variants_vcf,        // path(vcf)
+        ch_variants_tbi         // path(tbi)
+    )
+    ch_versions = ch_versions.mix(GATK4_GETPILEUPSUMMARIES.out.versions.first())
+
+    // Run CalculateContamination (tumor-only, no matched normal)
+    // Format: [meta, pileup_table, matched_normal_table]
+    // matched_normal_table is empty [] for tumor-only mode
+    ch_contamination_input = GATK4_GETPILEUPSUMMARIES.out.table
+        .map { meta, table -> [ meta, table, [] ] }
+
+    GATK4_CALCULATECONTAMINATION (
+        ch_contamination_input
+    )
+    ch_versions = ch_versions.mix(GATK4_CALCULATECONTAMINATION.out.versions.first())
+
+    emit:
+    contamination_table = GATK4_CALCULATECONTAMINATION.out.contamination
+    segmentation_table  = GATK4_CALCULATECONTAMINATION.out.segmentation
+    pileup_table        = GATK4_GETPILEUPSUMMARIES.out.table
+    versions            = ch_versions
+}
diff --git a/subworkflows/local/contamination_check/meta.yml b/subworkflows/local/contamination_check/meta.yml
new file mode 100644
index 000000000..ab7f5937b
--- /dev/null
+++ b/subworkflows/local/contamination_check/meta.yml
@@ -0,0 +1,41 @@
+name: contamination_check
+description: Estimate sample contamination using GATK GetPileupSummaries and CalculateContamination
+keywords:
+  - contamination
+  - QC
+  - GATK
+components:
+  - gatk4/getpileupsummaries
+  - gatk4/calculatecontamination
+input:
+  - ch_bam:
+      type: file
+      description: BAM files with their indices
+      pattern: "*.{bam,cram}"
+  - ch_fasta:
+      type: file
+      description: Reference genome FASTA file
+      pattern: "*.{fa,fasta}"
+  - ch_contamination_vcf:
+      type: file
+      description: VCF file containing common germline variants (gnomAD)
+      pattern: "*.vcf.gz"
+  - ch_intervals:
+      type: file
+      description: BED file with target intervals
+      pattern: "*.bed"
+output:
+  - contamination_table:
+      type: file
+      description: Table containing contamination estimates
+      pattern: "*.contamination.table"
+  - segmentation_table:
+      type: file
+      description: Table containing tumor segmentation
+      pattern: "*.segmentation.table"
+  - versions:
+      type: file
+      description: File containing software versions
+      pattern: "versions.yml"
+authors:
+  - "56053vujinovic"
diff --git a/subworkflows/local/contamination_check/tests/main.nf.test b/subworkflows/local/contamination_check/tests/main.nf.test
new file mode 100644
index 000000000..2909dccd7
--- /dev/null
+++ b/subworkflows/local/contamination_check/tests/main.nf.test
@@ -0,0 +1,112 @@
+nextflow_workflow {
+
+    name "Test Workflow CONTAMINATION_CHECK"
+    script "subworkflows/local/contamination_check/main.nf"
+    workflow "CONTAMINATION_CHECK"
+    tag "subworkflows"
+    tag "contamination_check"
+    config "./nextflow.config"
+
+    test("CONTAMINATION_CHECK - WGS, no intervals") {
+
+        when {
+            params {
+                outdir = "$outputDir"
+            }
+            workflow {
+                """
+                input[0] = channel.of(
+                    [
+                        [id:'earlycasualcaiman', sample:'earlycasualcaiman', single_end:false, sex:1, phenotype:1, case_id:'justhusky'],
+                        file(params.pipelines_testdata_base_path + 'testdata/earlycasualcaiman_sorted_md.bam', checkIfExists: true),
+                        file(params.pipelines_testdata_base_path + 'testdata/earlycasualcaiman_sorted_md.bam.bai', checkIfExists: true)
+                    ]
+                )
+                input[1] = channel.of([id:'genome'], file(params.pipelines_testdata_base_path + 'reference/reference.fasta', checkIfExists: true)).collect()
+                input[2] = channel.of([id:'genome'], file(params.pipelines_testdata_base_path + 'reference/reference.fasta.fai', checkIfExists: true)).collect()
+                input[3] = channel.of([id:'genome'], file(params.pipelines_testdata_base_path + 'reference/reference.dict', checkIfExists: true)).collect()
+                input[4] = channel.of(
+                    [
+                        file(params.pipelines_testdata_base_path + 'reference/grch37_gnomad_-r2.1.1-.vcf.gz', checkIfExists: true),
+                        file(params.pipelines_testdata_base_path + 'reference/grch37_gnomad_-r2.1.1-.vcf.gz.tbi', checkIfExists: true)
+                    ]
+                ).collect()
+                input[5] = Channel.empty()
+                """
+            }
+        }
+
+        then {
+            assertAll (
+                { assert workflow.success },
+                { assert snapshot(
+                        workflow.out.contamination_table
+                            .collect { it[1] }
+                            .flatten()
+                            .collect { file(it).name }
+                            .toSorted(),
+                        workflow.out.pileup_table
+                            .collect { it[1] }
+                            .flatten()
+                            .collect { file(it).name }
+                            .toSorted(),
+                        workflow.out.versions
+                    ).match()
+                }
+            )
+        }
+
+    }
+
+    test("CONTAMINATION_CHECK - WES, with intervals") {
+
+        when {
+            params {
+                outdir = "$outputDir"
+            }
+            workflow {
+                """
+                input[0] = channel.of(
+                    [
+                        [id:'earlycasualcaiman', sample:'earlycasualcaiman', single_end:false, sex:1, phenotype:1, case_id:'justhusky'],
+                        file(params.pipelines_testdata_base_path + 'testdata/earlycasualcaiman_sorted_md.bam', checkIfExists: true),
+                        file(params.pipelines_testdata_base_path + 'testdata/earlycasualcaiman_sorted_md.bam.bai', checkIfExists: true)
+                    ]
+                )
+                input[1] = channel.of([id:'genome'], file(params.pipelines_testdata_base_path + 'reference/reference.fasta', checkIfExists: true)).collect()
+                input[2] = channel.of([id:'genome'], file(params.pipelines_testdata_base_path + 'reference/reference.fasta.fai', checkIfExists: true)).collect()
+                input[3] = channel.of([id:'genome'], file(params.pipelines_testdata_base_path + 'reference/reference.dict', checkIfExists: true)).collect()
+                input[4] = channel.of(
+                    [
+                        file(params.pipelines_testdata_base_path + 'reference/grch37_gnomad_-r2.1.1-.vcf.gz', checkIfExists: true),
+                        file(params.pipelines_testdata_base_path + 'reference/grch37_gnomad_-r2.1.1-.vcf.gz.tbi', checkIfExists: true)
+                    ]
+                ).collect()
+                input[5] = Channel.fromPath(params.pipelines_testdata_base_path + 'reference/target.bed', checkIfExists: true).collect()
+                """
+            }
+        }
+
+        then {
+            assertAll (
+                { assert workflow.success },
+                { assert snapshot(
+                        workflow.out.contamination_table
+                            .collect { it[1] }
+                            .flatten()
+                            .collect { file(it).name }
+                            .toSorted(),
+                        workflow.out.pileup_table
+                            .collect { it[1] }
+                            .flatten()
+                            .collect { file(it).name }
+                            .toSorted(),
+                        workflow.out.versions
+                    ).match()
+                }
+            )
+        }
+
+    }
+
+}
diff --git a/subworkflows/local/contamination_check/tests/main.nf.test.snap b/subworkflows/local/contamination_check/tests/main.nf.test.snap
new file mode 100644
index 000000000..c9b91a552
--- /dev/null
+++ b/subworkflows/local/contamination_check/tests/main.nf.test.snap
@@ -0,0 +1,40 @@
+{
+    "CONTAMINATION_CHECK - WGS, no intervals": {
+        "content": [
+            [
+                "earlycasualcaiman_contamination.contamination.table"
+            ],
+            [
+                "earlycasualcaiman_pileups.pileups.table"
+            ],
+            [
+                "versions.yml:md5,46fc6219f36f2e8e436a824f3c0f9a4a",
+                "versions.yml:md5,dd08885235dcc7e9f408eba91ef7303e"
+            ]
+        ],
+        "timestamp": "2026-03-23T14:29:41.579345381",
+        "meta": {
+            "nf-test": "0.9.5",
+            "nextflow": "25.10.4"
+        }
+    },
+    "CONTAMINATION_CHECK - WES, with intervals": {
+        "content": [
+            [
+                "earlycasualcaiman_contamination.contamination.table"
+            ],
+            [
+                "earlycasualcaiman_pileups.pileups.table"
+            ],
+            [
+                "versions.yml:md5,46fc6219f36f2e8e436a824f3c0f9a4a",
+                "versions.yml:md5,dd08885235dcc7e9f408eba91ef7303e"
+            ]
+        ],
+        "timestamp": "2026-03-23T14:31:02.497064504",
+        "meta": {
+            "nf-test": "0.9.5",
+            "nextflow": "25.10.4"
+        }
+    }
+}
\ No newline at end of file
diff --git a/subworkflows/local/contamination_check/tests/nextflow.config b/subworkflows/local/contamination_check/tests/nextflow.config
new file mode 100644
index 000000000..3a5a56e5c
--- /dev/null
+++ b/subworkflows/local/contamination_check/tests/nextflow.config
@@ -0,0 +1,12 @@
+process {
+
+    withName: '.*CONTAMINATION_CHECK:GATK4_GETPILEUPSUMMARIES' {
+        ext.args = '--disable-sequence-dictionary-validation'
+        ext.prefix = { "${meta.id}_pileups" }
+    }
+
+    withName: '.*CONTAMINATION_CHECK:GATK4_CALCULATECONTAMINATION' {
+        ext.args = ''
+        ext.prefix = { "${meta.id}_contamination" }
+    }
+}
diff --git a/workflows/raredisease.nf b/workflows/raredisease.nf
index 7d7bd3d24..460a10366 100644
--- a/workflows/raredisease.nf
+++ b/workflows/raredisease.nf
@@ -27,13 +27,15 @@ include { SPRING_DECOMPRESS as SPRING_DECOMPRESS_TO_R1_FQ   } from '../modules/n
 include { SPRING_DECOMPRESS as SPRING_DECOMPRESS_TO_R2_FQ   } from '../modules/nf-core/spring/decompress/main'
 include { SPRING_DECOMPRESS as SPRING_DECOMPRESS_TO_FQ_PAIR } from '../modules/nf-core/spring/decompress/main'
 include { STRANGER                                          } from '../modules/nf-core/stranger/main'
-
 //
 // MODULE: Local modules
 //
 
 include { RENAME_ALIGN_FILES as RENAME_BAM } from '../modules/local/rename_align_files'
 include { RENAME_ALIGN_FILES as RENAME_BAI } from '../modules/local/rename_align_files'
+include { CREATE_HGNCIDS_FILE              } from '../modules/local/create_hgncids_file'
+include { CREATE_PEDIGREE_FILE             } from '../modules/local/create_pedigree_file'
+include { PARSE_CONTAMINATION              } from '../modules/local/parse_contamination/main'
 
 //
 // SUBWORKFLOWS
@@ -52,6 +54,7 @@ include { CALL_MOBILE_ELEMENTS                                        } from '..
 include { CALL_REPEAT_EXPANSIONS                                      } from '../subworkflows/local/call_repeat_expansions'
 include { CALL_SNV                                                    } from '../subworkflows/local/call_snv'
 include { CALL_STRUCTURAL_VARIANTS                                    } from '../subworkflows/local/call_structural_variants'
+include { CONTAMINATION_CHECK                                         } from '../subworkflows/local/contamination_check/main'
 include { GENERATE_CYTOSURE_FILES                                     } from '../subworkflows/local/generate_cytosure_files'
 include { GENS                                                        } from '../subworkflows/local/gens'
 include { PREPARE_REFERENCES                                          } from '../subworkflows/local/prepare_references'
@@ -294,7 +297,53 @@ workflow RAREDISEASE {
     )
     ch_versions = ch_versions.mix(QC_BAM.out.versions)
 
+    //
+    // SUBWORKFLOW: Check for contamination using GATK
+    //
+    ch_contamination_mqc = Channel.empty()
+
+    if (params.run_contamination && params.contamination_sites) {
+
+        log.info "=== CONTAMINATION CHECK ENABLED ==="
+        log.info "Analysis type: ${params.analysis_type}"
+
+        // Prepare contamination sites channel
+        ch_contamination_sites = Channel.of([
+            file(params.contamination_sites, checkIfExists: true),
+            file(params.contamination_sites_tbi, checkIfExists: true)
+        ]).collect()
+
+        // Prepare intervals channel - CRITICAL: Use Channel.empty() for WGS, not Channel.of([])
+        if (params.analysis_type == 'wes' && params.target_bed) {
+            ch_intervals_contamination = Channel.fromPath(params.target_bed).collect()
+            log.info "Using target BED for WES contamination check"
+        } else {
+            ch_intervals_contamination = Channel.empty()
+            log.info "No intervals for WGS contamination check (genome-wide)"
+        }
+
+        // Prepare BAM input with BAI
+        ch_bam_for_contamination = ch_mapped.genome_marked_bam
+            .join(ch_mapped.genome_marked_bai, failOnMismatch:true, failOnDuplicate:true)
 
+        CONTAMINATION_CHECK (
+            ch_bam_for_contamination,
+            ch_genome_fasta,
+            ch_genome_fai,
+            ch_genome_dictionary,
+            ch_contamination_sites,
+            ch_intervals_contamination
+        )
+
+        // Parse for MultiQC
+        PARSE_CONTAMINATION (
+            CONTAMINATION_CHECK.out.contamination_table
+        )
+
+        ch_contamination_mqc = PARSE_CONTAMINATION.out.mqc_table
+        ch_versions = ch_versions.mix(CONTAMINATION_CHECK.out.versions)
+        ch_versions = ch_versions.mix(PARSE_CONTAMINATION.out.versions)
+    }
 /*
 ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
     RENAME ALIGNMENT FILES FOR SMNCOPYNUMBERCALLER & REPEATCALLING
@@ -848,6 +897,9 @@ workflow RAREDISEASE {
     ch_multiqc_files = ch_multiqc_files.mix(QC_BAM.out.global_dist.map{_meta, reports -> reports}.collect().ifEmpty([]))
     ch_multiqc_files = ch_multiqc_files.mix(QC_BAM.out.cov.map{_meta, reports -> reports}.collect().ifEmpty([]))
     ch_multiqc_files = ch_multiqc_files.mix(QC_BAM.out.self_sm.map{_meta, reports -> reports}.collect().ifEmpty([]))
+    
+    // Add contamination results to MultiQC
+    ch_multiqc_files = ch_multiqc_files.mix(ch_contamination_mqc.map { _meta, file -> file })
 
     if (!skip_peddy) {
         ch_multiqc_files = ch_multiqc_files.mix(PEDDY.out.ped.map{_meta, reports -> reports}.collect().ifEmpty([]))