Summary & Overview

CPT 0471U: RAS Mutation Detection for Colorectal Cancer (PCR, FFPE)

CPT code 0471U designates a Proprietary Laboratory Analyses (PLA) test — the CRCdx® RAS Mutation Detection Kit from EntroGen Inc. — used to identify 35 specific KRAS and NRAS variants in colorectal cancer tissue. The code matters nationally because it captures a manufacturer-specific molecular diagnostic that informs targeted oncology care and payer coverage decisions. Its PLA status signals single-source ownership, which affects coding, reporting, and pricing transparency.

Key payers in the analysis include Aetna, Blue Cross Blue Shield, Cigna Health, UnitedHealthcare, and Medicare. Readers will find a concise clinical context for the test, a summary of typical sites of service, and an outline of common modifier usage relevant to laboratory services. The publication highlights what to expect in terms of coding classification, the clinical role of RAS mutation testing in colorectal cancer, and operational considerations for submitting claims using a PLA CPT code.

This overview is intended for national audiences including laboratory billing staff, oncology program administrators, and payer policy analysts seeking clear information on the coding and clinical context of a manufacturer-specific RAS mutation assay.

AetnaBlue Cross Blue ShieldCigna HealthUnitedHealthcareMedicare0471UCPTProprietary Laboratory Analysesmolecular diagnosticsKRASNRAScolorectal cancerPCR testing

Billing Code Overview

CPT code 0471U is a Proprietary Laboratory Analyses (PLA) code assigned exclusively to the CRCdx® RAS Mutation Detection Kit from EntroGen Inc. The test uses qualitative real–time polymerase chain reaction (PCR) to detect 35 specific variants in the KRAS and NRAS genes across exons 2, 3, and 4. The assay is performed on formalin–fixed paraffin–embedded (FFPE) tissue samples, which preserve tumor tissue for molecular analysis.

Service Type: Molecular pathology / companion diagnostic testing

Typical Site of Service: Clinical laboratory or reference molecular diagnostics laboratory

Clinical & Coding Specifications

Clinical Context

A 62-year-old patient with newly diagnosed metastatic colorectal adenocarcinoma undergoes surgical resection of the primary tumor. Formalin–fixed paraffin–embedded (FFPE) tumor tissue from the resection or diagnostic biopsy is sent to a reference molecular laboratory. The lab performs the CRCdx® RAS Mutation Detection Kit (EntroGen Inc.) using qualitative real‑time PCR to detect 35 KRAS and NRAS variants in exons 2, 3, and 4. The resulting RAS mutation status informs systemic therapy selection (for example, eligibility for anti‑EGFR monoclonal antibody therapy) and may be requested as part of a comprehensive molecular profile. Typical workflow steps: tissue accessioning and grossing at the surgical pathology or histology lab; FFPE sectioning and tumor enrichment if indicated; nucleic acid extraction and quality assessment; PCR assay using the proprietary CRCdx® kit; result interpretation by molecular pathology personnel; and report issuance to the treating oncologist. Typical site of service: outpatient hospital laboratory or independent reference molecular pathology laboratory. Service type: molecular oncology diagnostic test performed on FFPE tumor tissue.

Coding Specifications

Modifier	Description	When to Use
`00`	Default or not specified	Rarely used; indicates standard service when no other modifier applies.
`22`	Increased procedural services	When documentation supports significantly greater complexity in laboratory processing or interpretive effort beyond usual for the assay.
`26`	Professional component	When billing only the professional component (interpretation and report) separate from the technical component.
`52`	Reduced services	When test is partially performed with reduced scope (e.g., limited panel run due to tissue insufficiency).
`53`	Discontinued procedure	If testing was started but discontinued for documented technical failure or insufficient specimen.
`62`	Two surgeons/physicians	Not typically applicable but included when two pathologists share responsibility for interpretation.
`78`	Unplanned return to the operating/procedure room	Not applicable to laboratory testing; not typically used.
`80`	Assistant surgeon	Not applicable to lab services; seldom used for this procedure.
`82`	Assistant surgeon (when qualified resident not available)	Not applicable to lab services.
`TC`	Technical component	When billing only the technical component (laboratory processes, reagents, instrumentation) and not the professional interpretation.
`QK`	Qualified nonphysician laboratory director (high complexity)	When a qualified nonphysician directs the laboratory and meets payer-specific billing rules.
`QX`	Qualified nonphysician performing the service	When the nonphysician practitioner performed components and payer allows reporting.
`QY`	Qualified nonphysician technical component	When technical component is provided by a qualified nonphysician under payer rules.
`SH`	Diagnostic radiology, assistant at surgery	Not applicable to this lab test but included in broader modifier list.
`SJ`	Nurse practitioner, physician assistant, or clinical nurse specialist functioning as physician substitute	When applicable to supervision/ordering roles depending on payer policies.

Taxonomy Code	Specialty	Notes
2080P0206X	Anatomic and Clinical Pathology	Pathologists direct molecular testing and interpret results.
2080S0123X	Molecular Genetic Pathology	Specialty focused on molecular diagnostics for oncology.
207RC0000X	Medical Oncology	Oncologists order testing to guide systemic therapy decisions.
207Q00000X	Hematology/Oncology	Physicians managing colorectal cancer who request RAS testing.
363LF0000X	Clinical Laboratory Director	Laboratory directors overseeing assay validation and reporting.

Related Diagnoses

ICD-10 Code	Description	Clinical Relevance
`C18.9`	Malignant neoplasm of colon, unspecified	Common primary diagnosis prompting RAS mutation testing to guide systemic therapy.
`C19`	Malignant neoplasm of rectosigmoid junction	Tumors in this site undergo similar molecular testing for RAS status.
`C20`	Malignant neoplasm of rectum	Rectal adenocarcinoma specimens are tested for KRAS/NRAS mutations to inform treatment.
`C78.7`	Secondary malignant neoplasm of liver	Metastatic disease commonly prompts RAS testing on primary or metastatic tissue.
`Z85.038`	Personal history of malignant neoplasm of large intestine	Surveillance or recurrent disease evaluation may include molecular testing.

Related CPT Codes

CPT Code	Description	Relationship to This Procedure
`0471U`	CRCdx® RAS Mutation Detection Kit (EntroGen Inc.), qualitative real‑time PCR for 35 KRAS/NRAS variants (exons 2, 3, 4) on FFPE tissue	Primary PLA code for this specific proprietary assay; use for reporting the performed test and billing.
`81445`	Oncology (colon) multigene panel for tumor — selective hotspot analysis; interpretation and report	May be performed in parallel or instead of single‑gene RAS testing when broader genomic profiling is ordered.
`88305`	Level IV surgical pathology, gross and microscopic examination	Performed by the pathology service to process and evaluate the tumor specimen prior to molecular testing (tissue block selection, tumor percent assessment).
`88291`	Molecular pathology procedure, level I (e.g., PCR, targeted mutation analysis) — technical procedures	Represents technical molecular laboratory methods that may be billed when separate technical component coding applies depending on payer rules.
`0000U`	Data not available in the input.	Data not available in the input.

Beta

OpenPayer Beta

Summary & Overview

CPT 0471U: RAS Mutation Detection for Colorectal Cancer (PCR, FFPE)

AetnaBlue Cross Blue ShieldCigna HealthUnitedHealthcareMedicare0471UCPTProprietary Laboratory Analysesmolecular diagnosticsKRASNRAScolorectal cancerPCR testing

Billing Code Overview

Service Type: Molecular pathology / companion diagnostic testing

Typical Site of Service: Clinical laboratory or reference molecular diagnostics laboratory

Clinical & Coding Specifications

Clinical Context

Coding Specifications

Modifier	Description	When to Use
`00`	Default or not specified	Rarely used; indicates standard service when no other modifier applies.
`22`	Increased procedural services	When documentation supports significantly greater complexity in laboratory processing or interpretive effort beyond usual for the assay.
`26`	Professional component	When billing only the professional component (interpretation and report) separate from the technical component.
`52`	Reduced services	When test is partially performed with reduced scope (e.g., limited panel run due to tissue insufficiency).
`53`	Discontinued procedure	If testing was started but discontinued for documented technical failure or insufficient specimen.
`62`	Two surgeons/physicians	Not typically applicable but included when two pathologists share responsibility for interpretation.
`78`	Unplanned return to the operating/procedure room	Not applicable to laboratory testing; not typically used.
`80`	Assistant surgeon	Not applicable to lab services; seldom used for this procedure.
`82`	Assistant surgeon (when qualified resident not available)	Not applicable to lab services.
`TC`	Technical component	When billing only the technical component (laboratory processes, reagents, instrumentation) and not the professional interpretation.
`QK`	Qualified nonphysician laboratory director (high complexity)	When a qualified nonphysician directs the laboratory and meets payer-specific billing rules.
`QX`	Qualified nonphysician performing the service	When the nonphysician practitioner performed components and payer allows reporting.
`QY`	Qualified nonphysician technical component	When technical component is provided by a qualified nonphysician under payer rules.
`SH`	Diagnostic radiology, assistant at surgery	Not applicable to this lab test but included in broader modifier list.
`SJ`	Nurse practitioner, physician assistant, or clinical nurse specialist functioning as physician substitute	When applicable to supervision/ordering roles depending on payer policies.

Taxonomy Code	Specialty	Notes
2080P0206X	Anatomic and Clinical Pathology	Pathologists direct molecular testing and interpret results.
2080S0123X	Molecular Genetic Pathology	Specialty focused on molecular diagnostics for oncology.
207RC0000X	Medical Oncology	Oncologists order testing to guide systemic therapy decisions.
207Q00000X	Hematology/Oncology	Physicians managing colorectal cancer who request RAS testing.
363LF0000X	Clinical Laboratory Director	Laboratory directors overseeing assay validation and reporting.

Related Diagnoses

ICD-10 Code	Description	Clinical Relevance
`C18.9`	Malignant neoplasm of colon, unspecified	Common primary diagnosis prompting RAS mutation testing to guide systemic therapy.
`C19`	Malignant neoplasm of rectosigmoid junction	Tumors in this site undergo similar molecular testing for RAS status.
`C20`	Malignant neoplasm of rectum	Rectal adenocarcinoma specimens are tested for KRAS/NRAS mutations to inform treatment.
`C78.7`	Secondary malignant neoplasm of liver	Metastatic disease commonly prompts RAS testing on primary or metastatic tissue.
`Z85.038`	Personal history of malignant neoplasm of large intestine	Surveillance or recurrent disease evaluation may include molecular testing.

Related CPT Codes

CPT Code	Description	Relationship to This Procedure
`0471U`	CRCdx® RAS Mutation Detection Kit (EntroGen Inc.), qualitative real‑time PCR for 35 KRAS/NRAS variants (exons 2, 3, 4) on FFPE tissue	Primary PLA code for this specific proprietary assay; use for reporting the performed test and billing.
`81445`	Oncology (colon) multigene panel for tumor — selective hotspot analysis; interpretation and report	May be performed in parallel or instead of single‑gene RAS testing when broader genomic profiling is ordered.
`88305`	Level IV surgical pathology, gross and microscopic examination	Performed by the pathology service to process and evaluate the tumor specimen prior to molecular testing (tissue block selection, tumor percent assessment).
`88291`	Molecular pathology procedure, level I (e.g., PCR, targeted mutation analysis) — technical procedures	Represents technical molecular laboratory methods that may be billed when separate technical component coding applies depending on payer rules.
`0000U`	Data not available in the input.	Data not available in the input.