A commercially available antibody to proliferating cell nuclear antigen was used to characterize and compare proliferating cell populations in paraffin sections of benign, premalignant, and malignant lesions of human epidermis using routine immunohistochemical techniques. Three patterns emerged. An ordered pattern was found in prurigo nodularis and keratoacanthoma, wherein moderately and strongly positive nuclei were distributed in a continuous, basal-suprabasal layer of relatively uniform thickness. There was graded loss and ultimate extinction of PCNA staining in progressively more superficial epidermal cells. A basal dysplastic pattern was found in actinic keratosis and squamous cell carcinoma. Nuclei of essentially all dysplastic cells of both categories expressed PCNA, with a preponderance of strongly positive nuclei. These were localized to basal-suprabasal zones that were often expanded. Loss of PCNA reactivity toward the surface was often abrupt. Bowen's disease exhibited a diffuse dysplastic pattern, wherein large numbers of moderately and strongly positive nuclei, in random array, were present in essentially full thickness distribution. In many fields, however, a layer of cytologically bland basal cells, with faint or no nuclear staining, was interposed between dysplastic epithelium and dermis. This study has demonstrated that proliferating cell populations in epidermal lesions can be assessed with simple, inexpensive methods. There were consistent differences between the proliferating cell populations of the various entities studied, differences that can be reasonably correlated with other known clinical, microscopic, and biologic features of the lesions. This technique should provide an interesting new avenue for study of diverse cutaneous diseases.