A deeper understanding of the variance of epidermal cell proliferation may eventually increase the reproducibility of diagnostic classification. A prospective study of 46 consecutive, unselected biopsies from benign (keratoacanthoma n=14), premalignant (actinic keratosis n=15 and Bowen disease n=10) and malignant (squamous cell carcinoma n=7) skin lesions was studied to assess the presence and extent of differences in expression of the proliferation marker Ki-67 using a monoclonal antibody directed against a c-DNA defined subsegment (MIB-1) and a noncross-linking, proprietary fixative BoonFix. MIB-1 was expressed in the adjacent, non-affected skin in a scattered to confluent linear pattern in the basal/suprabasal cell layer. In actinic keratosis, MIB-1 expression, in addition to basal/suprabasal layers, extended to mid-zones of the epidermis. An interesting feature in actinic keratosis as well as in Bowen disease was the expression of MIB-1 in the epithelium lining the hair follicles. In Bowen disease, MIB-1 was observed throughout the full thickness of the epidermis, unequivocally separating this entity from others under study. In invasive squamous cell carcinoma, MIB-1 expression was not consistent between and within cases. MIB-1 positivity was variably found in all layers of the epidermis, but showed a chaotic and haphazard pattern with total loss of polarity. Keratoacanthoma cases showed highly variable MIB-1 expression, ranging from no expression to expression in both basal/suprabasal and mid-zone layers of the epidermis. These results warrant further study of modulation of cell proliferation in actinic keratosis.