Recently we demonstrated that the keratin 17 (K17) content exceeded the K16 content in most follicular tumors, in comparison with non-follicular epithelial skin tumours by two-dimensional gel electrophoresis (2-DE), densitometry and immunohistochemistry. At present the origin of basal cell carcinoma (BCC) is unknown. So, based on the above results, we studied keratin expression in eight cases of BCC, in order to analyze tumor differentiation by both biochemical and immunohistochemical methods. Biochemically, using 2-DE and immunoblotting, stratified epithelial keratins K5/K14 and large amounts of K17 were present in all cases. Simple epithelial keratins K8 and K19 were expressed in all and half of the cases, respectively. However, hyperproliferative associated keratins (K6/K16) and keratinized keratins (K1/K10) were detected in only a few cases. Immunohistochemical studies using frozen sections with chain-specific antikeratin monoclonal antibodies against K1, K7, K8, K10, K14, K16, K17, K18 and K19 showed that BCC tumor cells reacted positively with antibodies against K8, K14, K17 and K19, but did not react, or were rarely positive with K1, K7, K10, K16 and K18 antibodies. Predominant expression of K17 and the frequent expression of K8 and K19, with little K6/K16 and K1/K10 expression are the characteristic features of BCC, suggesting that BCC is differentiated towards undifferentiated follicular epithelia, most probably hair bulge cells.