Using viable cells of a human squamous‐cell carcinoma (SCC) cell line as immunogen, we generated 2 monoclonal antibodies, MAbs K984 and K928, to SCC surface antigens. Immunoperoxidase staining of frozen sections of normal epidermis revealed that MAb K984 reacts with the poorly differentiated basal cells, while MAb K928 is reactive with the more highly differentiated suprabasal cells. A similar complementary reaction pattern of these antibodies was demonstrated in the majority of well‐differentiated human tumors and some moderately differentiated SCCs. In contrast, simultaneous reactivity of MAb K984 and K928 was found for the majority of cells within other well‐and moderately differentiated SCCs, as well as all poorly differentiated SCCs. Further biochemical characterization indicated that the antigen recognized by MAb K984 is similar to the one recognized by MAb SF‐25. MAb K928 recognizes a 50‐to 55‐kDa molecule under non‐reducing conditions. Antibodies with similar features to MAb K928 have not been described previously. The antigens recognized by MAbs K984 and K928 can be regarded as novel markers associated with cellular maturation in squamous epithelia. The antigen detected by MAb K984 is probably associated with the proliferating fraction in SCCs.