KL-6 classified as Cluster 9 (MUC-I) is a circulating high-molecular-weight mucin-like molecule. Serum level of KL-6 was measured by a sandwich assay using KL-6 antibody as not only a catcher but also as a tracer. We established 2 additional monoclonal antibodies (MAbs), LISA 101 and EH-123, reacting with KL-6 epitopes different from the epitope recognized by KL-6 antibody. The KL-6-associated mucins detected by the sandwich assay using LISA 101 or EH-123 antibody as a catcher and KL-6 antibody as a tracer were designated as LISA 1-6 and CAM 123-6 respectively. The diagnostic values as the serum markers of KL-6, LISA 1-6 and CAM 123-6 were evaluated measuring their levels in the same serum from healthy individuals and from patients with pulmonary, pancreatic and breast adenocarcinomas. KL-6 was increased abnormally at high rates of more than 50% in pancreatic cancer and in benign lung diseases, LISA 1-6 only in pancreatic cancer, and CAM 123-6 only in pulmonary adenocarcinoma. In benign lung diseases, however, LISA 1-6 and CAM 123-6 were increased abnormally at the rates of only 5.3% and 0% respectively. These observations clearly indicate that LISA 1-6 and CAM 123-6 constitute a part of KL-6, but that they are superior to KL-6 as tumor markers for pancreatic cancer and for pulmonary adenocarcinoma respectively, because of their much lower false-positive rates.