Uterine carcinosarcoma histologically comprises the components of epithelial and mesenchymal malignancies, and is known to be clinically highly aggressive. To reveal the significance of the expression of tyrosine-kinase-receptor-type oncoproteins in this tumor type, the incidence and distribution of the KIT, EGFR, and HER-2 (c-erbB-2) oncoproteins were immunohistochemically examined in 16 surgically resected cases. For 6 cases, the EGFR and HER-2 amplifications were also examined by fluorescence in situ hybridization (FISH). In the epithelial component, overexpressions of KIT, EGFR, and HER-2 were detected in 4 (25%), 5 (31%), and 9 (56%) cases, respectively, whereas these overexpressions in the mesenchymal component were detected in 6 (38%), 8 (50%), and 1 (6%) cases, respectively. KIT and EGFR were co-overexpressed in the mesenchymal component of 4 cases and in the epithelial component of 2 cases. However, HER-2 overexpression was mostly detected in the epithelial component only, and tended to occur independently of KIT and/or EGFR overexpression. By FISH, one of the 4 cases with HER-2 overexpression showed low-level gene amplification. In two cases with EGFR overexpression, the gain of EGFR alleles and/or polyploidization of chromosome 7 had occurred. The expression patterns of KIT, EGFR, and HER-2 differed between the epithelial and mesenchymal components, and the regulation of their expression appeared important in the acquisition of mesenchymal metaplasia in uterine carcinosarcoma. Structural and/or numerical alterations of chromosomes might be in part involved in EGFR and/or HER-2 overexpression in this tumor type.