A human monoclonal antibody, BM2, was produced by a hybridoma line generated by fusion of lymph node cells from a patient with squamous cell carcinoma (SCC) of the tongue with human B-lymphoblastoid cell line HO-323. BM2, an IgM class antibody, was reactive with all of the SCC cell lines tested. Frozen sections of normal and malignant tumor specimens were investigated to examine the reactivity of BM2 towards them. All 35 oral SCC specimens reacted with BM2. Normal stratified squamous epithelium showed positive staining in basal cells, but no staining was seen in other layers of the stratified epithelium, simple epithelium, and tissues of nonepithelial origin. Ductal basal cells of normal salivary gland also showed positive staining. Western blotting and immunoprecipitation analysis revealed that BM2 recognized 52 kDa membrane-associated protein. BM2 may therefore be a useful tool for biological and clinical studies of SCC.