The expression and topography of some integrins and basement membrane proteins in cutaneous basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs) have been studied by immunohistochemistry and Western blotting. It has been shown that the typical cell-to-cell distribution of alpha 2 beta 1 and alpha 3 beta 1 found in normal epidermis is replaced by pericellular distribution in both BCC and SCC cells. BCC and SCC also showed different patterns of expression of alpha 6 beta 4, an integrin heterodimer normally lining the basal surface of basal epidermal keratinocytes: whereas SCC showed high expression and pericellular distribution of alpha 6 beta 4, BCC cells did not express this integrin at all. The absence of alpha 6 and beta 4 subunits from BCC extracts was confirmed by Western blotting. The molecular composition of the basement membrane was markedly different in the two types of epidermal tumors. Whereas laminin and collagen type IV were conserved in the basement membrane zone of both tumors, the molecular complex BM-600/nicein, which is recognized by the monoclonal antibody GB3 and is possibly identical to the previously described basement membrane glycoproteins kalinin and epiligrin, was absent from BCC cells. Then, the simultaneous loss of expression of alpha 6 beta 4 and BM-600/nicein in BCC cells but not in SCC cells indicates that alpha 6 beta 4 integrin and one of its potential ligands may be co-regulated in both BCC and SCC, thus suggesting a role for this phenomenon in the pathogenesis and clinical behavior of these epidermal tumors.