Origin of basal cell carcinoma (BCC) is still unclear. We studied the cytokeratin (CK) profile in BCC using monoclonal antibodies against 12 CKs to further investigate the suggested origin of the tumor from follicular matrix cells or from follicular outer root sheath cells and to determine if BCC subtypes can be identified on the basis of their CK profiles. Cases of pilomatricoma and samples of fetal skin served as controls to establish the CK profile in matrical cells and developing follicles during intrauterine life, that of the epidermis and cutaneous adnexa in adult life having been determined in a previous study. The most significant findings were as follows: (a) CK 5 and CK 17 positivity in all the BCCs studied; (b) CK 7, CK 8, CK 18, and CK 19 positivity in 30/52, 33/52, 42/52, and 14/52 BCCs, respectively; (c) CK 14 negativity in almost all the BCCs studied; and (d) lack of CK 1 expression only in 2/2 morpheiform BCCs and 4/10 nodular BCCs. The study suggests a tumorous differentiation toward follicular outer root sheath cells and, in most cases, also toward the glandular components of the pilosebaceous-apocrine unit. No significant difference in the CK profile among the BCC subtypes studied was found.