Lesions originating from different types of skin cells differ significantly with respect to their pathologic importance. The aim of this work was to examine as to what extent the differences in the origin are reflected in expression levels of CDK-2 and to investigate whether CDK-2 expression might be considered as potential marker useful for diagnostics and assessment of invasiveness of human nonmelanocytic lesions. We conducted comparative immunohistochemical studies of expression of cyclin-dependent kinase 2 (CDK-2) in 16 benign epithelial skin lesions, 11 precancerous lesions, 19 cases of basal cell carcinoma (first such study), 14 squamous cell carcinomas (SCCs), and 7 fibromas. Development of benign epithelial skin lesions was not associated with considerable increase of the CDK-2 expression. Increase of the CDK-2 level was observed in precancerous lesions, and the expression was strongest in SCCs. The level of CDK-2 may be related to invasiveness of skin cancers, as squamous cell carcinomas expressed the enzyme significantly stronger than basal cell carcinomas. Higher percentage fraction of CDK-2 positive cells observed in SCC compared with precancerous lesions may be useful for histopathologic diagnostics of this cancer. Moreover, strong immunohistochemical CDK-2 staining of the cancer cells present deep in dermis may facilitate their detection in histopathologic examinations.