Summary & Overview

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.

AetnaBlue Cross Blue ShieldCigna HealthUnitedHealthcareMedicare0464UCPTProprietary Laboratory Analysescolorectal cancer screeningstool DNA testmolecular diagnosticslaboratoryCologuard Plus

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

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.