CPT 0506U: EndoSign® Barrett’s Esophagus DNA Methylation Test

CPT code 0506U is a Proprietary Laboratory Analyses (PLA) code that specifically reports the EndoSign® Barrett’s Esophagus Test by Cyted Health Inc., a next-generation sequencing-based assay that analyzes DNA methylation patterns in esophageal cells to generate a likelihood score for Barrett’s esophagus; service type: laboratory molecular diagnostic testing; typical site of service: outpatient laboratory or reference diagnostic laboratory.

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CPT 0506U: EndoSign® Barrett’s Esophagus DNA Methylation Test

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Sign up for cpt 0506U policy alerts

Get alerted when payer policies referencing 0506U are released or updated.

Monitor payer policy activity

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

Clinical & Coding Specifications

Clinical Context

A 55‑year‑old patient with chronic gastroesophageal reflux symptoms and endoscopic suspicion of Barrett’s esophagus provides an esophageal cell sample via brush or biopsied tissue collected during upper endoscopy. The sample is sent to a clinical laboratory that performs the EndoSign® Barrett’s Esophagus Test (Cyted Health Inc.), a next‑generation sequencing–based DNA methylation assay that produces a likelihood score for Barrett’s esophagus. The clinical workflow includes order entry by the gastroenterologist, collection of the specimen during EGD (esophagogastroduodenoscopy), specimen labeling and shipment to the performing laboratory, processing and sequencing in a certified molecular pathology lab, generation of the EndoSign® report, and transmission of results to the ordering provider for use in surveillance and management decisions. Typical site of service is an outpatient endoscopy suite, ambulatory surgical center, or hospital outpatient department, with laboratory processing performed at the proprietary testing laboratory.

Related CPT Codes

CPT Code	Description	Relationship to This Procedure
`43235`	Upper gastrointestinal endoscopy including biopsy, single or multiple	Often performed immediately before specimen collection for EndoSign®; provides tissue or brush samples
`88305`	Surgical pathology, gross and microscopic examination	May be used when formal biopsy specimens are submitted to pathology in addition to molecular testing
`81479`	Unlisted molecular pathology procedure	Occasionally used for reporting proprietary or novel molecular tests when a PLA code is not available; for EndoSign® use `0506U` instead
`0506U`	EndoSign® Barrett’s Esophagus Test (proprietary PLA)	Specific PLA code to report the EndoSign® methylation sequencing assay performed by Cyted Health Inc.
`99000`	Handling and/or conveyance of specimen for transfer from the physician to a laboratory	Used when specimen handling for off‑site testing incurs additional billable services

Related Modifiers

5 rows

Modifier	Description	When to Use
26	Modifier 26 (Professional Component) identifies and bills only the professional portion of a split service — the physician’s interpretation, report, and medical judgment — when the technical…	- Use CPT Modifier -26 when you are billing only the professional component (PC) of a split‑bill eligible service—i.e., you performed the physician interpretation, medical judgment and prepared a…
52	Modifier ‑52 (Reduced Services) indicates that a service or procedure was partially reduced or omitted at the provider’s discretion, allowing reporting of the basic procedure number with a qualifier…	- Use modifier -52 when a physician or qualified health professional electively reduces or omits part of a procedure or service (for example, performing fewer required views or omitting a portion of…
53	Modifier 53 (Discontinued Procedure) signals that a surgical or diagnostic service was begun by the physician but terminated because of extenuating circumstances that threatened the patient’s…	- Use modifier -53 when a physician/qualified healthcare professional has started a surgical or diagnostic procedure (e.g., anesthesia administered, incision or scope insertion) and then discontinues…
59	Modifier 59 indicates a distinct procedural service when two procedures that are not normally billed together are clinically and procedurally separate. The CPT definition (as reiterated by CMS)…	- Use modifier -59 to report a distinct procedural service when documentation supports that the procedure reported is not normally billed together with another service on the same day because of a…
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Related Provider Taxonomies

8 rows

Taxonomy Code	Specialty	Notes
2086S0105X	Surgery of the Hand (Surgery) Physician	A surgeon with expertise in the investigation, preservation and restoration by medical, surgical and rehabilitative means, of all structures of the up…
207L00000X	Anesthesiology Physician	An anesthesiologist is trained to provide pain relief and maintenance, or restoration, of a stable condition during and immediately following an opera…
208D00000X	General Practice Physician	A physician who specializes in the general practice of diagnosing, treating, and managing patients with a variety of illnesses and conditions.
3336M0002X	Mail Order Pharmacy	A pharmacy where pharmacists compound or dispense prescriptions or other medications in accordance with federal and state law, using common carriers t…
2085R0204X	Vascular & Interventional Radiology Physician	A radiologist who diagnoses and treats diseases by various radiologic imaging modalities. These include fluoroscopy, digital radiography, computed tom…
3336C0003X	Community/Retail Pharmacy	A pharmacy where pharmacists store, prepare, and dispense medicinal preparations and/or prescriptions for a local patient population in accordance wit…
363LP0222X	Critical Care Pediatric Nurse Practitioner	Physician Assistants & Advanced Practice Nursing Providers · Nurse Practitioner
224ZR0403X	Driving and Community Mobility Occupational Therapy Assistant	Occupational therapy assistants contribute to the completion of an individualized occupational therapy driving and community mobility evaluation by ad…

Related ICD-10-CM Codes

25 rows

ICD-10-CM Code	Description
C15.3	Malignant neoplasm of upper third of esophagus
C15.9	Malignant neoplasm of esophagus, unspecified
D12.6	Benign neoplasm of colon, unspecified
K21.9	Gastro-esophageal reflux disease without esophagitis
K22.0	Achalasia of cardia
K22.2	Esophageal obstruction
K22.3	Perforation of esophagus
K25.9	Gastric ulcer, unspecified as acute or chronic, without hemorrhage or perforation
K26.9	Duodenal ulcer, unspecified as acute or chronic, without hemorrhage or perforation
K29.70	Gastritis, unspecified, without bleeding

Showing 1–10 of 25

Related Payer Policy Updates

Specialty: Genetic & Molecular Testing1 / 3

10 rows

Policy	Payer	Effective Date
RTM Testing of Homocysteine Metabolism-Related Conditions	Oscar Health	2026-10-01
Multimarker Serum Testing Related to Ovarian Cancer	Blue Cross Blue Shield - Rhode Island	2026-09-01
Genomic Profiling for Selecting Targeted Cancer Therapies	Blue Cross Blue Shield - Rhode Island	2026-09-01
Whole Exome and Whole Genome Sequencing for Diagnosis of Genetic Disorders	Blue Cross Blue Shield - Rhode Island	2026-09-01
Biomarker and Genetic/Molecular Testing Coverage and Prior Authorization	Blue Cross Blue Shield - Rhode Island	2026-09-01
Non-Invasive Prenatal Testing (NIPT)	univerahealthcare	2026-08-17
Lumizyme (alglucosidase alfa) — Pompe Disease (acid alpha‑glucosidase deficiency)	Cigna	2026-08-15
Molecular Oncology Testing for Solid Tumor Cancer Diagnosis, Prognosis, and Treatment Decisions	Colorado Rocky Mountain Health Plans	2026-08-01
Molecular Oncology Testing for Hematologic Cancer Diagnosis, Prognosis, and Treatment Decisions	Colorado Rocky Mountain Health Plans	2026-08-01
Carrier Testing Panels for Genetic Diseases	Colorado Rocky Mountain Health Plans	2026-08-01

CPT 0001U: PreciseType HEA Erythrocyte Antigen Genotyping

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

CPT 0002U: PolypDX™ Urine Metabolomic Risk Assay

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

CPT 0003U: Overa (MIA2G) Ovarian Cancer Risk Assay

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

CPT 0005U: ExosomeDx Prostate (IntelliScore) urine gene expression 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 Gene Panel

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: 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 Transcripts

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.

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

Related CPT Codes

CPT Code	Description	Relationship to This Procedure
`43235`	Upper gastrointestinal endoscopy including biopsy, single or multiple	Often performed immediately before specimen collection for EndoSign®; provides tissue or brush samples
`88305`	Surgical pathology, gross and microscopic examination	May be used when formal biopsy specimens are submitted to pathology in addition to molecular testing
`81479`	Unlisted molecular pathology procedure	Occasionally used for reporting proprietary or novel molecular tests when a PLA code is not available; for EndoSign® use `0506U` instead
`0506U`	EndoSign® Barrett’s Esophagus Test (proprietary PLA)	Specific PLA code to report the EndoSign® methylation sequencing assay performed by Cyted Health Inc.
`99000`	Handling and/or conveyance of specimen for transfer from the physician to a laboratory	Used when specimen handling for off‑site testing incurs additional billable services

Related Modifiers

5 rows

Modifier	Description	When to Use
26	Modifier 26 (Professional Component) identifies and bills only the professional portion of a split service — the physician’s interpretation, report, and medical judgment — when the technical…	- Use CPT Modifier -26 when you are billing only the professional component (PC) of a split‑bill eligible service—i.e., you performed the physician interpretation, medical judgment and prepared a…
52	Modifier ‑52 (Reduced Services) indicates that a service or procedure was partially reduced or omitted at the provider’s discretion, allowing reporting of the basic procedure number with a qualifier…	- Use modifier -52 when a physician or qualified health professional electively reduces or omits part of a procedure or service (for example, performing fewer required views or omitting a portion of…
53	Modifier 53 (Discontinued Procedure) signals that a surgical or diagnostic service was begun by the physician but terminated because of extenuating circumstances that threatened the patient’s…	- Use modifier -53 when a physician/qualified healthcare professional has started a surgical or diagnostic procedure (e.g., anesthesia administered, incision or scope insertion) and then discontinues…
59	Modifier 59 indicates a distinct procedural service when two procedures that are not normally billed together are clinically and procedurally separate. The CPT definition (as reiterated by CMS)…	- Use modifier -59 to report a distinct procedural service when documentation supports that the procedure reported is not normally billed together with another service on the same day because of a…
[object Object]

Related Provider Taxonomies

8 rows

Taxonomy Code	Specialty	Notes
2086S0105X	Surgery of the Hand (Surgery) Physician	A surgeon with expertise in the investigation, preservation and restoration by medical, surgical and rehabilitative means, of all structures of the up…
207L00000X	Anesthesiology Physician	An anesthesiologist is trained to provide pain relief and maintenance, or restoration, of a stable condition during and immediately following an opera…
208D00000X	General Practice Physician	A physician who specializes in the general practice of diagnosing, treating, and managing patients with a variety of illnesses and conditions.
3336M0002X	Mail Order Pharmacy	A pharmacy where pharmacists compound or dispense prescriptions or other medications in accordance with federal and state law, using common carriers t…
2085R0204X	Vascular & Interventional Radiology Physician	A radiologist who diagnoses and treats diseases by various radiologic imaging modalities. These include fluoroscopy, digital radiography, computed tom…
3336C0003X	Community/Retail Pharmacy	A pharmacy where pharmacists store, prepare, and dispense medicinal preparations and/or prescriptions for a local patient population in accordance wit…
363LP0222X	Critical Care Pediatric Nurse Practitioner	Physician Assistants & Advanced Practice Nursing Providers · Nurse Practitioner
224ZR0403X	Driving and Community Mobility Occupational Therapy Assistant	Occupational therapy assistants contribute to the completion of an individualized occupational therapy driving and community mobility evaluation by ad…

Related ICD-10-CM Codes

25 rows

ICD-10-CM Code	Description
C15.3	Malignant neoplasm of upper third of esophagus
C15.9	Malignant neoplasm of esophagus, unspecified
D12.6	Benign neoplasm of colon, unspecified
K21.9	Gastro-esophageal reflux disease without esophagitis
K22.0	Achalasia of cardia
K22.2	Esophageal obstruction
K22.3	Perforation of esophagus
K25.9	Gastric ulcer, unspecified as acute or chronic, without hemorrhage or perforation
K26.9	Duodenal ulcer, unspecified as acute or chronic, without hemorrhage or perforation
K29.70	Gastritis, unspecified, without bleeding

Showing 1–10 of 25

Related Payer Policy Updates

Specialty: Genetic & Molecular Testing1 / 3

10 rows

Policy	Payer	Effective Date
RTM Testing of Homocysteine Metabolism-Related Conditions	Oscar Health	2026-10-01
Multimarker Serum Testing Related to Ovarian Cancer	Blue Cross Blue Shield - Rhode Island	2026-09-01
Genomic Profiling for Selecting Targeted Cancer Therapies	Blue Cross Blue Shield - Rhode Island	2026-09-01
Whole Exome and Whole Genome Sequencing for Diagnosis of Genetic Disorders	Blue Cross Blue Shield - Rhode Island	2026-09-01
Biomarker and Genetic/Molecular Testing Coverage and Prior Authorization	Blue Cross Blue Shield - Rhode Island	2026-09-01
Non-Invasive Prenatal Testing (NIPT)	univerahealthcare	2026-08-17
Lumizyme (alglucosidase alfa) — Pompe Disease (acid alpha‑glucosidase deficiency)	Cigna	2026-08-15
Molecular Oncology Testing for Solid Tumor Cancer Diagnosis, Prognosis, and Treatment Decisions	Colorado Rocky Mountain Health Plans	2026-08-01
Molecular Oncology Testing for Hematologic Cancer Diagnosis, Prognosis, and Treatment Decisions	Colorado Rocky Mountain Health Plans	2026-08-01
Carrier Testing Panels for Genetic Diseases	Colorado Rocky Mountain Health Plans	2026-08-01

CPT 0001U: PreciseType HEA Erythrocyte Antigen Genotyping

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

CPT 0002U: PolypDX™ Urine Metabolomic Risk Assay

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

CPT 0003U: Overa (MIA2G) Ovarian Cancer Risk Assay

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

CPT 0005U: ExosomeDx Prostate (IntelliScore) urine gene expression 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 Gene Panel

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: 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 Transcripts

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.

OpenPayer

CPT 0506U: EndoSign® Barrett’s Esophagus DNA Methylation Test

Sign up for cpt 0506U policy alerts

OpenPayer

CPT 0506U: EndoSign® Barrett’s Esophagus DNA Methylation Test

Sign up for cpt 0506U policy alerts

Clinical & Coding Specifications

Clinical Context

Related CPT Codes

Related Modifiers

Related Provider Taxonomies

Related ICD-10-CM Codes

Related Payer Policy Updates

Related Codes

References

Clinical & Coding Specifications

Clinical Context

Related CPT Codes

Related Modifiers

Related Provider Taxonomies

Related ICD-10-CM Codes

Related Payer Policy Updates

Related Codes

References

CPT 0506U: EndoSign® Barrett’s Esophagus DNA Methylation Test

Sign up for cpt 0506U policy alerts

CPT 0506U: EndoSign® Barrett’s Esophagus DNA Methylation Test

Sign up for cpt 0506U policy alerts

Clinical & Coding Specifications

Clinical Context

Related CPT Codes

Related Modifiers

Related Provider Taxonomies

Related ICD-10-CM Codes

Related Payer Policy Updates

Related Codes

What does CPT code 0506U represent?

How is the EndoSign® specimen collected and where is the test performed?

How does 0506U relate to other CPT codes like 43235, 88305, or 81479?

Which modifiers are specified for reporting 0506U and when are they used?

Are payers and reimbursement details for 0506U provided on this page?

References

Clinical & Coding Specifications

Clinical Context

Related CPT Codes

Related Modifiers

Related Provider Taxonomies

Related ICD-10-CM Codes

Related Payer Policy Updates

Related Codes

What does CPT code 0506U represent?

How is the EndoSign® specimen collected and where is the test performed?

How does 0506U relate to other CPT codes like 43235, 88305, or 81479?

Which modifiers are specified for reporting 0506U and when are they used?

Are payers and reimbursement details for 0506U provided on this page?

References