Although KIT and EGFR overexpressions are reported to occur in breast cancer, their pathological significance is still unclear. We examined KIT, EGFR, and c-erbB-2 overexpressions immunohistochemically in 150 cases of surgically resected breast cancer and their correlation with the histological type and grade and mesenchymal and/or myoepithelial immunophenotype of primary tumors. To facilitate the analysis, we constructed a tissue microarray comprising 2-mm diameter tissues cored from the representative tissue block of each tumor. KIT, EGFR, and c-erbB-2 overexpressions were detected in 15 (10%), 12 (8%), and 23 (15%), respectively. The KIT was more frequent in the group comprising comedo-type ductal carcinoma in situ and invasive ductal carcinomas (IDCs) of the solid-tubular subtype than in the group of other histological types (P=0.027), and the EGFR was more frequent in IDCs of solid-tubular type than in other histological types (P <0.05). KIT and EGFR overexpressions were correlated with nuclear grade 3 (P=0.0095 and 0.0005) and tended to be concurrent (P=0.005). KIT overexpression was correlated with vimentin and S-100 expression (P=0.003 and P=0.005), and EGFR overexpression was correlated with S100 expression (P=0.0001). These correlations with grade and mesenchymal/myoepithelial markers were not observed for c-erbB-2 overexpression. KIT and EGFR appeared to be indicators of high-grade breast carcinoma groups that often contain the carcinomas with mesenchymal and/or myoepithelial differentiation, which are distinct from the group with c-erbB-2 overexpression.