The E-cadherin-beta-catenin complex regulates the architectural integrity of epithelia by mediating intercellular adhesion. Down-regulation of its expression may contribute to invasion and metastatic behavior of carcinoma cells. Several studies demonstrated an abnormal expression of E-cadherin, beta-catenin, or both in various carcinomas, including non-melanoma skin cancer. The aim of the present study was to investigate the involvement of E-cadherin-catenin adhesion system in the progression of human cutaneous squamous cell carcinoma (SCC). For that purpose, sections from normal skin, skin showing solar elastosis (SE), solar keratosis (SK), and SCC were stained with monoclonal antibodies against E-cadherin and beta-catenin. Evaluation of the staining results was performed using a semi-quantitative method in which pattern and intensity of staining, percentage of positive cells, and cytoplasmic staining were evaluated. Normal skin and skin showing mild and moderate solar elastosis strongly expressed membranous E-cadherin and beta-catenin. E-cadherin expression was progressively reduced in the epidermis of skin with severe solar elastosis through solar keratosis to SCC. The same phenomenon was observed for beta-catenin starting from solar keratosis. In some cases of SCC, additional cytoplasmic staining was observed. We found no correlation between E-cadherin and beta-catenin expression and tumor differentiation or between SCC from sun-exposed and sun-protected skin. Statistical analysis revealed correlation between expression of both E-cadherin and beta-catenin and the morphology of the lesion. These results support a gradual evolution from severely sun-damaged skin to SCC, not only on a morphologic level, but also at the molecular level.