Abnormal control of the cell cycle is closely linked to carcinogenesis. p21[supWAF1/CIP1] protein is a universal inhibitor of G1 cyclin-dependent kinase and is induced by p53-dependent and -independent pathways. In order to elucidate the role of p21[supWAF1/CIP1] in human skin carcinogenesis, protein expression in squamous cell carcinoma (SCC), basal cell carcinoma (BCC), Bowen's disease (BD), actinic keratosis (AK), keratoacanthoma (KA), seborrheic keratosis (SK), and normal skin was examined using an immunohistochemical method. In normal skin, a few positive cells were seen in some cases in the upper spinous layer of the epidermis; sebaceous glands also had positive cells. In cases of SK and KA, positive cells were found in the basal and suprabasal epidermal layers (proliferation pattern), and in cases of BD and AK, positive cells were seen mainly in the upper spinous layer (differentiation pattern). Cases of SCC had more positive cells and showed two staining patterns: proliferation, or mixed. Cases of BCC had no positive cells. p2l[supWAF1/CIP1] has some unidentified role in keratinocyte tumorigenesis, which may not be related directly to carcinogenesis. [ABSTRACT FROM AUTHOR]