An IgM class monoclonal antibody (MAb) was derived by immunizing BALB/c mice with a human endometrial carcinoma cell line. This MAb, termed C12, exhibited strong reactivity against endometrial carcinoma, but lesser reactivity against normal endometria. The antigen recognized by MAb C12 (C12 antigen) was detected by radiometric assay in sera from patients with various carcinomas, but not in sera from patients without carcinomas or in sera from normal individuals. MAb C12 was found to agglutinate blood type O erythrocytes, but not A, B, or AB erythrocytes. To clarify the specificity of MAb C12, tissue staining experiments were performed in parallel using MAb C12, Ulex europaeus lectin I (anti-H), and a monoclonal anti-H antibody. In endometrial carcinoma tissues, both H and C12 antigens increased, but the C12 antigen showed a prominent increase, in contrast to the H antigen. Further, the C12 antigen was not found in endothelial cells of blood type O patients. In sera, the level of the H antigen varied according to the host's blood type. The sera from blood type O individuals possessed higher levels of the H antigen than those with blood type A or B. Thus, the H antigen showed no value as a tumor-associated serum marker. In contrast, the presence of the C12 antigen in sera was not determined by ABO blood group status. Thus, MAb C12 was demonstrated to be a unique MAb that reacts with an H-like antigen occurring in the sera of patients with carcinomas irrespective of ABO blood group status. MAb C12 may prove to be a useful marker for cancer patient serum.