Squamous differentiation occurs in 25 to 50% of endometrial endometrioid adenocarcinomas. In this study, we analyzed the immunohistochemical expression and localization of beta- and gamma-catenin, molecular changes in the beta-catenin gene, and the subcellular localization of the desmosomal component protein, desmoplakin, by laser scanning microscopy in 35 endometrial carcinomas with squamous differentiation. In the glandular component, beta-catenin showed nuclear localization in 10 of 35 (28.5%) samples, whereas in the squamous component, nuclear localization was found in 15 of 35 (42.9%). Of the 15 samples that showed nuclear localization of beta-catenin in the squamous component, seven samples (46.7%) did not express gamma-catenin. The phenomenon was not correlated with mutation in exon 3 region of beta-catenin gene. Furthermore, in these samples, there was diffuse cytoplasmic staining for desmoplakin. These observations have not been reported in other tumors. Our results suggest that unique molecular events, i.e., stimulation of beta-catenin and suppression of gamma-catenin expression, occur within endometrial carcinomas with squamous differentiation.