Basal cell carcinoma and squamous cell carcinoma are common entities in clinical practice. Their distinction can be difficult clinically as well as histologically. CD10 or common acute lymphoblastic leukemia antigen (CALLA) is a metallomembrane endopeptidase expressed on a variety of normal and neoplastic cells. We sought to determine if the CD10 immunostain could have diagnostic utility in distinguishing between early superficial basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). CD10 was strongly expressed in 14 out of 14 superficial BCCs and failed to express in 2 out of 2 deeply infiltrative BCCs. CD10 was negative in the tumor cells in 13 out of 13 superficially invasive SCCs and SCC in situ. CD10 expressed weakly in the surrounding stromal cells of 2 out of 13 SCCs. These findings support the utility of CD10 as a marker for early BCC, especially when SCC cannot be excluded clinically or by conventional stains. Furthermore, these results implicate CD10 in the pathogenesis of BCC.