In EACs with Barrett's esophagus (BE), HER2 positivity was significantly associated with improved DSS [HR = 0.54 (95% CI: 0.35–0.84), P = 0.0065] and overall survival (P = 0.0022) independent of pathologic features but was not prognostic among EACs without BE. This evidence concerns the gene ERBB2 and esophageal adenocarcinoma.