A positive circumferential resection margin (CRM) is associated with poor survival after esophagectomy for cancer. The Royal College of Pathologists (RCP) defines a CRM when tumor is found <1 mm of the lateral margin whereas the College of American Pathologists (CAP) defines CRM when tumor cells are located at the lateral margin. This study evaluates the clinical prognostic significance of CRM on overall survival (OS) and disease-free survival (DFS) in patients who underwent esophagectomy for T3 esophageal adenocarcinoma. Analysis included 132 patients. CRM was found in 26 cases (19.7%) corresponding to CAP criteria versus 89 cases (67.4%) corresponding to RCP criteria. Median OS using RCP criteria was 16.4 (95%CI, 8.5-24.2) months for CRM patients versus 21.0 (95%CI 16.3-25.6) months in CRM patients (P=0.144). With CAP criteria, median OS in CRM and CRM patients was 9.4 (95%CI, 7.6-11.2) months versus 21.6 (95%CI, 18.9-24.3) months, respectively (P=0.000). Median DFS using RCP criteria was 18.0 (95%CI, 11.5-24.6) months for CRM patients versus 11.0 (95%CI, 8.1-14.0) months for CRM patients (P=0.257). Applying the CAP criteria, median DFS in CRM and CRM patients was 16.3 (95%CI, 10.6-22.0) months versus 7.0 (95%CI, 6.3-7.8) months, respectively (P=0.000). Effects of a CRM according to CAP criteria remained significant after multivariate testing [OS: hazard ratio (HR), 2.43; 95%CI, 1.52-3.90; DFS: HR, 2.09; 95%CI, 1.32-3.30]. Only with the CAP criteria, CRM is an independent prognostic factor for survival and recurrence in patients with T3 adenocarcinoma of the esophagus. The circumferential margin should only be considered positive (ie, R1) if the tumor is found at the inked lateral margin of resection in accordance with the CAP criteria.