-catenin regulates cadherin-mediated cell-cell adhesion and also functions as a signaling molecule. In this study, we examined the expression pattern of E-cadherin, ␣-catenin and -catenin in 22 cases of esophageal squamous-cell carcinoma by Western-blot analysis. Expression of E-cadherin, ␣-catenin and -catenin was lower in carcinomas than in normal esophageal mucosa in 4 cases (18.2%) for E-cadherin, 6 cases (27.3%) for ␣-catenin and 9 cases (40.9%) for -catenin. Expression of -catenin was not always correlated with that of E-cadherin. Over-expression of -catenin was observed in 3 cases (13.6%). Of 3 cases that presented with over-expression of -catenin, 2 showed cytoplasmic staining by immunohistochemistry. Nuclear localization of -catenin was observed in one case that had higher -catenin level in tumor tissue (1.4-fold higher than normal mucosa). The genomic DNA sequences of the -catenin and the APC gene were analyzed. No mutation of the -catenin gene was observed in any cases. Silent mutation of the APC gene was found in all the cases that showed over-expression or nuclear localization of the -catenin protein. These results indicate that alterations of the cadherin-catenin complex may play an important role in a sub-set of esophageal carcinogenesis. Furthermore, it is suggested that -catenin over-expression is not caused by genetic alteration of either the -catenin or the APC gene. Int.