Basal cell carcinoma with matrical differentiation is an extremely rare variant. To date, only 12 cases have been described in the literature. This tumor is a typical basal cell carcinoma with basaloid nests containing shadow cells identical to those of pilomatricoma and pilomatrical carcinoma. We present two additional cases and have investigated the immunoprofile of .-catenin and osteopontin with the aim of determining both their biological significance and possible diagnostic utility. The morphological and immunohistochemical features of these cases that we have found suggest that basal cell carcinomas with matrical differentiation belong to a spectrum of lesions deriving from hair follicles in which .-catenin plays an important role in the tumor development, differentiation, and behavior.