The aberrant expression of embryonic simple epithelial keratins K8 and K18 has been previously detected in chemically-induced mouse skin carcinomas and in cultured epidermal keratinocytes containing H-ras oncogenes. In this study, we report that cell lines derived from benign papillomas do not generally synthesize simple epithelial keratins, regardless of the presence of H-ras gene alterations. These results reinforce our previous suggestion that the expression of these keratins during mouse epidermal carcinogenesis is a marker of malignant transformation. The comparison of the two-dimensional electrophoresis intermediate filament protein profiles of transformed keratinocytes in culture, reveal that during in vitro progression to the malignant phenotype increased synthesis of simple epithelial keratins is associated to a general disturbance on the expression of cytoskeletal proteins.