Background: Early cancer (high-grade dysplasia [HGD] and intramucosal carcinoma [ImCa]) associated with Barrett's esophagus (BE) may have a circumferential spatial predilection. Objective: To describe the esophageal circumferential location of early cancer in BE. Design and Setting: Retrospective study, single tertiary referral center. Patients and Intervention: One hundred nineteen patients were referred for endoscopic eradication therapy for early cancer associated with BE. Endoscopic images and reports and pathology were reviewed. Main Outcome Measurements: Circumferential location designation of early cancer in BE by using a clock-face orientation. Results: One hundred nineteen of 131 patients referred for endoscopic eradication therapy had a location designation for their advanced histology (91.9%). There were a total of 57 patients (47.9%) with HGD and 62 patients (52.1%) with ImCa. There was a significantly higher rate of early cancer (HGD or ImCa) in the right hemisphere (12 to 6 o'clock location) compared with the left hemisphere (84.9% vs 15.1%, P <.0001). The highest percentage of early cancer was found in the 12 to 3 o'clock quadrant (64.7%); 71.9% of HGD and 58.1% of ImCa lesions were located in the 12 to 3 o'clock quadrant. Limitations: Retrospective design, single center. Conclusions: Early cancer associated with BE is far more commonly found in the right hemisphere of the esophagus (12 to 6 o'clock) with the highest rate in the 12 to 3 o'clock quadrant. These findings support enhanced scrutiny of the right hemisphere of the esophagus during surveillance and endoscopic treatment of patients with BE. Copyright © 2013 by the American Society for Gastrointestinal Endoscopy.