Using a panel of monoclonal and polyclonal antibodies raised against human carcinoembryonic antigen (CEA) and CEA-related molecules, we detected strong expression of an antigen, with immunoreactivity consistent with non-specific cross-reacting antigen (NCA) (CD66c), in all of 26 normal human nail specimens obtained from various fingers and toes. In longitudinal sections, strong and constant expression of the NCA-like antigen was seen on keratinocytes distributed in the upper epithelial cell layers of the nail bed, while in transverse sections the expression was limited to the major central portions of the nail bed, but only where longitudinal epidermal ridges were observed. In the hyponychium and the ventral aspect of the proximal nail fold, the expression was weak or lacking. No expression was seen in the nail matrix, the nail plate, or the dorsal aspect of the proximal nail fold. The same results were obtained for all of the 26 nails studied. This report is the first to demonstrate that an antigen of the CEA family, with NCA-like immunoreactivity, is expressed in a specific subpopulation of keratinocytes in the nail bed. The specific expression pattern suggests that the antigen may play a part in adhesion of the nail plate to the nail bed.