Four mixed Merkel cell and squamous cell carcinomas of the skin are described. The patients ranged in age from 74 to 90 years and demonstrated or had a history of previous ultraviolet or infrared damage to the skin, manifested by basal cell carcinoma, squamous cell carcinoma, actinic keratoses, solar elastosis, and erythema ab igne. Light microscopic examination of all 4 cases revealed invasive neoplasms consisting of 2 distinct but admixed cell types. The predominant cell type was consistent with Merkel cell carcinoma and was characterized by scant cytoplasm, a small dark polygonal nucleus with granular chromatin, a high mitotic rate, and cytokeratin 20 positivity. In each case, the Merkel cell component merged with a cytokeratin 20 negative squamous component characterized by abundant eosinophilic cytoplasm, intercellular bridges, and keratinization with focal squamous pearl formation. Immunohistochemical staining patterns were consistent with the usual pattern for that cell type; transitional cells were not demonstrated. The intimate admixture of the 2 antigenically different neoplastic cell types, and common etiologic role of ultraviolet and possibly infrared damage, lend support to the theory that some Merkel cell carcinomas and squamous cell carcinomas may arise from a pluripotent epidermal stem cell. (J Am Acad Dermatol 1998;39:882-7.)