BACKGROUND: Epidermal cell adhesion and basement membrane (BM) are essential for the differentiated structure of squamous epithelium, and both are reduced in malignant tumours. MATERIALS AND METHODS: We analysed the expression of cell adhesion-related proteins desmoplakin and E-cadherin, BM components laminin and collagen IV, and BM receptor integrin alpha 6 in experimental preneoplastic changes and neoplasms of skin. Different mouse strains (NMRI, C57Bl/6 and DBA/2) and exposure protocols (DMBA, UV, DMBA + UV) were used to find possible differences in the expression of cell adhesion and BM proteins within individual tumour types. RESULTS: The individual strain had an impressive role on the expression of tumors. The exposure model affected the type of tumour found and tumour behaviour. The location and expression of cell attachment proteins were dependent on morphology, but mouse strain and type of exposure had no effect. The decline in the expression of markers studied was gradual involving the cytoplasmic immunoreactivity of integrin alpha 6 and laminin observed in dysplastic epidermis, BM structure formation becoming increasingly disturbed in dysplasia; this was present in squamous cell carcinomas and absent in undifferentiated tumours. Desmoplakin expression gradually disappeared during the decline in differentiation. E-cadherin expression was preserved longer, and disappeared along with the loss of squamous properties. CONCLUSIONS: Desmoplakin and E-cadherin served in this study as differentiation markers. None of these proteins seem to explain the differences in the tumour sensitivity of individual mouse strains.