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CPT 0464U: Cologuard Plus™ Stool DNA Colorectal Cancer Screening

Headline: New CPT code 0464U designates Cologuard Plus™ — a stool DNA and blood-based colorectal cancer screening assay.

CPT code 0464U represents a Proprietary Laboratory Analyses (PLA) code assigned to Cologuard Plus™ from Exact Sciences Laboratories LLC, a stool-based molecular screening test that evaluates DNA markers (LASS4, LRRC4, PPP2R5C, with reference marker ZDHHC1) and fecal blood to produce a positive or negative result for colorectal cancer risk. Nationally, this code matters because it standardizes reporting for a manufacturer-specific screening assay that may affect laboratory billing workflows, screening program tracking, and payer coverage assessments.

Key payers covered in this analysis include Aetna, Blue Cross Blue Shield, Cigna Health, UnitedHealthcare, and Medicare. Readers will find a concise overview of what the code denotes, the clinical context for stool-based colorectal cancer screening, typical sites of service, and which payers are included in the coverage review. The publication also summarizes benchmarks and policy-relevant details to inform billing teams, laboratorians, and health plan policy analysts about coding consistency and administrative implications.

This summary is intended for a national audience and does not provide clinical recommendations or state-specific guidance.

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Billing Code Overview

CPT code 0464U is a Proprietary Laboratory Analyses (PLA) code that applies exclusively to a single laboratory test: Cologuard Plus™ from Exact Sciences Laboratories LLC. The test analyzes a stool sample for DNA markers (including LASS4, LRRC4, and PPP2R5C, with reference marker ZDHHC1) and for blood in the stool. Results are processed by an algorithm that reports a positive or negative screen for colorectal cancer risk based on the levels of those markers.

Service type: Laboratory — molecular stool-based colorectal cancer screening test

Typical site of service: Clinical laboratory or reference laboratory; sample collection occurs at home with patient-collected stool specimen

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CPT 0464U: Cologuard Plus™ Stool DNA Colorectal Cancer Screening

Headline: New CPT code 0464U designates Cologuard Plus™ — a stool DNA and blood-based colorectal cancer screening assay.

This summary is intended for a national audience and does not provide clinical recommendations or state-specific guidance.

Customize your policy alerts

Sign up for cpt 0464U policy alerts

Get alerted when payer policies referencing 0464U are released or updated.

Monitor payer policy activity

Receive email alerts as soon as relevant payer policies are published or updated.

Billing Code Overview

Service type: Laboratory — molecular stool-based colorectal cancer screening test

Typical site of service: Clinical laboratory or reference laboratory; sample collection occurs at home with patient-collected stool specimen

Clinical & Coding Specifications

Clinical Context

A typical patient is a 50–75 year-old adult eligible for colorectal cancer (CRC) screening who receives a Cologuard Plus™ kit from a primary care clinic or gastroenterology practice. The clinician discusses screening options (colonoscopy, FIT, multi-target stool DNA) and documents informed choice; the patient elects the multi-target stool DNA test. The provider orders the test, the laboratory kit is shipped to the patient’s home, and the patient collects a stool sample per manufacturer instructions and returns it to Exact Sciences Laboratories LLC. The lab analyzes stool for DNA markers including LASS4, LRRC4, PPP2R5C, a reference marker ZDHHC1, and fecal immunochemical test (FIT) hemoglobin. Results are processed through the proprietary algorithm and reported as positive or negative for increased CRC risk. Positive results prompt clinician notification and referral for diagnostic colonoscopy; negative results are documented and routine screening interval is communicated. Typical site of service is outpatient clinic, patient home (sample collection), and clinical laboratory performing testing.

Coding Specifications

Modifier	Description	When to Use
`00`	No modifier—default reporting	Use when no special circumstances apply.
`22`	Increased procedural services	Rarely applicable; use only if additional, documented work is performed beyond standard reporting requirements (e.g., extensive interpretation/reporting beyond routine algorithm output).
`52`	Reduced services	Use if testing was partially performed or incomplete with documented reason (billing reduced service).
`53`	Discontinued procedure	Use if specimen collection/testing was aborted prior to completion with documentation.
`59`	Data not provided in the input.	Data not available in the input.
`62`	Two surgeons	Data not provided in the input.
`78`	Unplanned return to OR	Data not provided in the input.
`80`	Assistant surgeon	Data not provided in the input.
`AS`	Physician assistant, nurse practitioner, or clinical nurse specialist services	Use when an APP documents and manages ordering/follow-up for the test under full scope and billing rules require `AS` for non-physician practitioner rendering services.
`TC`	Technical component	Use to report the technical component of testing when the performing laboratory bills only for the technical component separate from professional interpretation.
`QK`	Medical direction of two, three, or four concurrent anesthesia procedures by the same physician	Data not provided in the input.
`QX`	Qualified nonphysician anesthetist with medical direction	Data not provided in the input.
`QY`	Medical direction of one certified registered nurse anesthetist (CRNA) by an anesthesiologist	Data not provided in the input.

Taxonomy Code	Specialty	Notes
207Q00000X	Family Medicine	Primary care clinicians commonly order CRC screening including multi-target stool DNA tests.
207R00000X	Internal Medicine	Primary care internists order and manage screening and follow-up referral.
207L00000X	Gastroenterology	Gastroenterologists review positive results and perform diagnostic colonoscopy.
261QR0400X	Clinical Laboratory/Pathology	Laboratory specialists oversee test processing and reporting at the performing lab.
363LP0800X	Nurse Practitioner	NPs often coordinate screening orders, patient education, and result follow-up.

Related Diagnoses

ICD-10 Code	Description	Clinical Relevance
`Z12.11`	Encounter for screening for malignant neoplasm of colon	Standard screening encounter for colorectal cancer; primary reason for ordering `0464U`.
`Z12.12`	Encounter for screening for malignant neoplasm of rectum	Screening of rectal malignancy risk using stool DNA/FIT testing.
`R19.5`	Other fecal abnormalities	Symptom that may prompt noninvasive stool testing when patients report abnormal stool.
`R19.7`	Diarrhea, unspecified	Symptom that can affect stool testing interpretation or prompt diagnostic evaluation.
`K92.1`	Melena	Overt gastrointestinal bleeding sign that may require FIT component consideration and further diagnostic workup.
`Z80.0`	Family history of malignant neoplasm of digestive organs	Family history elevates CRC risk and supports screening with multi-target stool DNA testing.
`Z85.038`	Personal history of malignant neoplasm of large intestine	Prior CRC history that influences surveillance strategy; may prompt different testing intervals.
`K50.90`	Crohn's disease, unspecified, without complications	Inflammatory bowel disease patients have altered screening and surveillance needs; stool DNA test utility varies.

Related CPT Codes

CPT Code	Description	Relationship to This Procedure
`0464U`	Cologuard Plus™ stool DNA and FIT analysis; proprietary PLA code for Exact Sciences Laboratories LLC	Primary test code for the multi-target stool DNA colorectal cancer screening assay—used to report the laboratory screening service.
`G0105`	Colorectal cancer screening; fecal occult blood test, home blood stool test kit (patient provided)	Alternative screening method (FIT/FOBT) that may be offered or previously used; not billed concurrently with `0464U` for same screening episode.
`G0121`	Colorectal cancer screening; fecal occult blood test, single specimen	Related screening alternative; documents other non-invasive stool testing options.
`45378`	Colonoscopy, flexible; diagnostic, including collection of specimen(s) by brushing or washing, when performed (with or without biopsy)	Diagnostic procedure performed after a positive `0464U` result to evaluate and obtain tissue.
`88305`	Level IV surgical pathology, gross and microscopic examination	Pathology code for evaluation of biopsy specimens obtained at colonoscopy following a positive screening test.
`80053`	Comprehensive metabolic panel (CMP)	Representative laboratory tests that may be ordered in pre-procedural evaluation prior to colonoscopy after a positive screening result.

CPT 0001U: PreciseType HEA Multiplex Erythrocyte Antigen Assay

CPT-0002U-POLYPDX-URINE-METABOLOMIC-ASSAY-ADENOMATOUS-POLYP-RISK

CPT 0002U: Urine Metabolomic Polyp Risk Assay (PolypDX™)

CPT-0003U-OVAR-A-NEXT-GENERATION-OVARIAN-CANCER-RISK-ASSAY

CPT 0003U: Overa™ (OVA1 Next Generation) Ovarian Cancer Risk Assay

CPT-0005U-PROSTATE-EXOSOMEDX-INTELLISCORE-GENE-EXPRESSION-URINE-TEST

CPT 0005U: ExosomeDx Prostate (IntelliScore) Urine Gene Expression Risk Test

CPT-0007U-TOXPROTECT-URINE-DRUG-SCREEN-WITH-DNA-AUTHENTICATION

CPT 0007U: ToxProtect Urine Drug Screen with DNA Authentication

CPT-0008U-H-PYLORI-ANTIBIOTIC-RESISTANCE-SEQUENCING-PANEL

CPT 0008U: H. pylori Antibiotic Resistance Panel, Gene Sequence Analysis

CPT-0009U-DEPARRAY-HER2-FISH-TUMOR-CELL-ISOLATION

CPT 0009U: DEPArray HER2 Tumor‑Cell Isolation with FISH Analysis

CPT-0010U-BACTERIAL-TYPING-WHOLE-GENOME-SEQUENCING-MAYO-CLINIC

CPT 0010U: Bacterial Typing by Whole Genome Sequencing, Mayo Clinic

CPT-0011U-CORDANT-CORE-ALGORITHMIC-ORAL-FLUID-DRUG-TEST

CPT 0011U: Cordant CORE™ Oral Fluid Drug Test with Algorithmic Steady‑State Comparison

CPT-0016U-BCR-ABL1-MAJOR-MINOR-FUSION-TRANSCRIPT-TESTING

CPT 0016U: BCR–ABL1 Major and Minor Breakpoint Fusion Transcript Testing

Showing 1–10 of 536

Frequently Asked Questions

References

1.CPT® Codes and Descriptions. AAPC. Retrieved Aug 11, 2026.Maintains the CPT code set's official descriptions and guidelines, licensed from the American Medical Association, used as the definitional source for CPT codes on this page.
2.HCPCS Quarterly Update. Centers for Medicare & Medicaid Services (CMS). Retrieved Aug 11, 2026.CMS's quarterly release of HCPCS Level II codes and short/long descriptors, the source for HCPCS code definitions and update history.
3.ICD-10-CM Full Code List. Centers for Medicare & Medicaid Services (CMS). Retrieved Aug 11, 2026.CMS's complete ICD-10-CM diagnosis code list, used to cross-reference diagnosis codes associated with this procedure or service.

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Trek Health ingests and normalizes Transparency in Coverage data and payer policy updates to give provider organizations a clear view of how commercial reimbursement behaves across markets, payers, and services. Our platform transforms raw payer disclosures into structured intelligence that supports contract evaluation, payer negotiations, and service line strategy. By combining market benchmarks with ongoing policy visibility, Trek helps teams identify variability, risk, and opportunity in commercial reimbursement. The result is faster insight, stronger negotiating positions, and more informed financial decisions.

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Clinical & Coding Specifications

Clinical Context

Coding Specifications

Modifier	Description	When to Use
`00`	No modifier—default reporting	Use when no special circumstances apply.
`22`	Increased procedural services	Rarely applicable; use only if additional, documented work is performed beyond standard reporting requirements (e.g., extensive interpretation/reporting beyond routine algorithm output).
`52`	Reduced services	Use if testing was partially performed or incomplete with documented reason (billing reduced service).
`53`	Discontinued procedure	Use if specimen collection/testing was aborted prior to completion with documentation.
`59`	Data not provided in the input.	Data not available in the input.
`62`	Two surgeons	Data not provided in the input.
`78`	Unplanned return to OR	Data not provided in the input.
`80`	Assistant surgeon	Data not provided in the input.
`AS`	Physician assistant, nurse practitioner, or clinical nurse specialist services	Use when an APP documents and manages ordering/follow-up for the test under full scope and billing rules require `AS` for non-physician practitioner rendering services.
`TC`	Technical component	Use to report the technical component of testing when the performing laboratory bills only for the technical component separate from professional interpretation.
`QK`	Medical direction of two, three, or four concurrent anesthesia procedures by the same physician	Data not provided in the input.
`QX`	Qualified nonphysician anesthetist with medical direction	Data not provided in the input.
`QY`	Medical direction of one certified registered nurse anesthetist (CRNA) by an anesthesiologist	Data not provided in the input.

Taxonomy Code	Specialty	Notes
207Q00000X	Family Medicine	Primary care clinicians commonly order CRC screening including multi-target stool DNA tests.
207R00000X	Internal Medicine	Primary care internists order and manage screening and follow-up referral.
207L00000X	Gastroenterology	Gastroenterologists review positive results and perform diagnostic colonoscopy.
261QR0400X	Clinical Laboratory/Pathology	Laboratory specialists oversee test processing and reporting at the performing lab.
363LP0800X	Nurse Practitioner	NPs often coordinate screening orders, patient education, and result follow-up.

Related Diagnoses

ICD-10 Code	Description	Clinical Relevance
`Z12.11`	Encounter for screening for malignant neoplasm of colon	Standard screening encounter for colorectal cancer; primary reason for ordering `0464U`.
`Z12.12`	Encounter for screening for malignant neoplasm of rectum	Screening of rectal malignancy risk using stool DNA/FIT testing.
`R19.5`	Other fecal abnormalities	Symptom that may prompt noninvasive stool testing when patients report abnormal stool.
`R19.7`	Diarrhea, unspecified	Symptom that can affect stool testing interpretation or prompt diagnostic evaluation.
`K92.1`	Melena	Overt gastrointestinal bleeding sign that may require FIT component consideration and further diagnostic workup.
`Z80.0`	Family history of malignant neoplasm of digestive organs	Family history elevates CRC risk and supports screening with multi-target stool DNA testing.
`Z85.038`	Personal history of malignant neoplasm of large intestine	Prior CRC history that influences surveillance strategy; may prompt different testing intervals.
`K50.90`	Crohn's disease, unspecified, without complications	Inflammatory bowel disease patients have altered screening and surveillance needs; stool DNA test utility varies.

Related CPT Codes

CPT Code	Description	Relationship to This Procedure
`0464U`	Cologuard Plus™ stool DNA and FIT analysis; proprietary PLA code for Exact Sciences Laboratories LLC	Primary test code for the multi-target stool DNA colorectal cancer screening assay—used to report the laboratory screening service.
`G0105`	Colorectal cancer screening; fecal occult blood test, home blood stool test kit (patient provided)	Alternative screening method (FIT/FOBT) that may be offered or previously used; not billed concurrently with `0464U` for same screening episode.
`G0121`	Colorectal cancer screening; fecal occult blood test, single specimen	Related screening alternative; documents other non-invasive stool testing options.
`45378`	Colonoscopy, flexible; diagnostic, including collection of specimen(s) by brushing or washing, when performed (with or without biopsy)	Diagnostic procedure performed after a positive `0464U` result to evaluate and obtain tissue.
`88305`	Level IV surgical pathology, gross and microscopic examination	Pathology code for evaluation of biopsy specimens obtained at colonoscopy following a positive screening test.
`80053`	Comprehensive metabolic panel (CMP)	Representative laboratory tests that may be ordered in pre-procedural evaluation prior to colonoscopy after a positive screening result.

CPT 0001U: PreciseType HEA Multiplex Erythrocyte Antigen Assay

CPT-0002U-POLYPDX-URINE-METABOLOMIC-ASSAY-ADENOMATOUS-POLYP-RISK

CPT 0002U: Urine Metabolomic Polyp Risk Assay (PolypDX™)

CPT-0003U-OVAR-A-NEXT-GENERATION-OVARIAN-CANCER-RISK-ASSAY

CPT 0003U: Overa™ (OVA1 Next Generation) Ovarian Cancer Risk Assay

CPT-0005U-PROSTATE-EXOSOMEDX-INTELLISCORE-GENE-EXPRESSION-URINE-TEST

CPT 0005U: ExosomeDx Prostate (IntelliScore) Urine Gene Expression Risk Test

CPT-0007U-TOXPROTECT-URINE-DRUG-SCREEN-WITH-DNA-AUTHENTICATION

CPT 0007U: ToxProtect Urine Drug Screen with DNA Authentication

CPT-0008U-H-PYLORI-ANTIBIOTIC-RESISTANCE-SEQUENCING-PANEL

CPT 0008U: H. pylori Antibiotic Resistance Panel, Gene Sequence Analysis

CPT-0009U-DEPARRAY-HER2-FISH-TUMOR-CELL-ISOLATION

CPT 0009U: DEPArray HER2 Tumor‑Cell Isolation with FISH Analysis

CPT-0010U-BACTERIAL-TYPING-WHOLE-GENOME-SEQUENCING-MAYO-CLINIC

CPT 0010U: Bacterial Typing by Whole Genome Sequencing, Mayo Clinic

CPT-0011U-CORDANT-CORE-ALGORITHMIC-ORAL-FLUID-DRUG-TEST

CPT 0011U: Cordant CORE™ Oral Fluid Drug Test with Algorithmic Steady‑State Comparison

CPT-0016U-BCR-ABL1-MAJOR-MINOR-FUSION-TRANSCRIPT-TESTING

CPT 0016U: BCR–ABL1 Major and Minor Breakpoint Fusion Transcript Testing

Showing 1–10 of 536

Frequently Asked Questions

References

1.CPT® Codes and Descriptions. AAPC. Retrieved Aug 11, 2026.Maintains the CPT code set's official descriptions and guidelines, licensed from the American Medical Association, used as the definitional source for CPT codes on this page.
2.HCPCS Quarterly Update. Centers for Medicare & Medicaid Services (CMS). Retrieved Aug 11, 2026.CMS's quarterly release of HCPCS Level II codes and short/long descriptors, the source for HCPCS code definitions and update history.
3.ICD-10-CM Full Code List. Centers for Medicare & Medicaid Services (CMS). Retrieved Aug 11, 2026.CMS's complete ICD-10-CM diagnosis code list, used to cross-reference diagnosis codes associated with this procedure or service.

Published by

Trek Health powers OpenPayer with a leading commercial payer intelligence platform, seamlessly converting fragmented payer data into actionable insights for provider organizations.

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CPT 0464U: Cologuard Plus™ Stool DNA Colorectal Cancer Screening

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Billing Code Overview

OpenPayer

CPT 0464U: Cologuard Plus™ Stool DNA Colorectal Cancer Screening

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Billing Code Overview

Clinical & Coding Specifications

Clinical Context

Coding Specifications

Related Diagnoses

Related CPT Codes

Related Codes

References

Clinical & Coding Specifications

Clinical Context

Coding Specifications

Related Diagnoses

Related CPT Codes

Related Codes

References

CPT 0464U: Cologuard Plus™ Stool DNA Colorectal Cancer Screening

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Billing Code Overview

CPT 0464U: Cologuard Plus™ Stool DNA Colorectal Cancer Screening

Sign up for cpt 0464U policy alerts

Billing Code Overview

Clinical & Coding Specifications

Clinical Context

Coding Specifications

Related Diagnoses

Related CPT Codes

Related Codes

What does CPT 0464U represent?

Which biomarkers and result format are used in Cologuard Plus reported under 0464U?

Where is the 0464U service performed and how is the technical component billed?

What related CPT codes should I be aware of when billing or reviewing a 0464U claim?

Which ICD-10 diagnosis codes are relevant when reporting 0464U?

References

Clinical & Coding Specifications

Clinical Context

Coding Specifications

Related Diagnoses

Related CPT Codes

Related Codes

What does CPT 0464U represent?

Which biomarkers and result format are used in Cologuard Plus reported under 0464U?

Where is the 0464U service performed and how is the technical component billed?

What related CPT codes should I be aware of when billing or reviewing a 0464U claim?

Which ICD-10 diagnosis codes are relevant when reporting 0464U?

References