The expression of human carcinoma-associated antigen (HCA), a mucin-type glycoprotein, was assessed in 50 esophagogastrectomy specimens. Areas, each from different cases, of Barrett esophagus (n = 36), low-grade dysplasia (n = 38), high-grade dysplasia/carcinoma in situ (n = 26), and esophageal adenocarcinoma (EAC; n = 34) were examined by immunohistochemical stains to 2 anti-HCA monoclonal antibodies, G1 and HAE3. These two antibodies showed similar staining patterns. HCA was overexpressed significantly in EAC and high-grade dysplasia/carcinoma in situ compared with benign esophageal mucosa (P < .001 for both), Barrett esophagus (P < .001 for both), and low-grade dysplasia (P < .025 for both). HCA overexpression did not correlate with the grade of EAC (P > .1). The results suggest that overexpression of HCA might help in diagnosing esophageal dysplasia and cancer. The correlation of HCA with the grade of esophageal dysplasia suggests its possible involvement in the pathogenesis of EAC. HCA also might provide a target for immunotherapy.