MUC1, membrane-associated mucins, has various types based on different glycoforms in its extracellular domain and is widely expressed in gastrointestinal tissues. Many investigations have showed that aberrant expression of MUC1 in gastrointestinal cancer tissue has clinicopathological and biological importance in cancer disease. KL-6 mucin, one kind of MUC1, was also investigated and suggested to have a significant relationship with a worse tumor behavior especially cancer cell invasion and metastasis in various gastrointestinal cancers. On the other hand, clinicopathological availability of KL-6 mucin varied among each gastrointestinal cancer. In colorectal and gastric cancer, circumferential membrane and/or cytoplasmic localization of KL-6 mucin were frequently detected in the cancer tissue of patients with the presence of deeper invasion and lymph node metastasis of cancer cells. Therefore, the subcellular localization of KL-6 mucin in cancer tissues can be used for predicting a worse outcome for patients. In primary liver cancer, KL-6 mucin expression was detected in cholangiocarcinoma but not in hepatocellular carcinoma tissues. Therefore, it can be used as a good marker for discriminating cholangiocarcinoma from hepatocellular carcinoma. While various significant clinicopathological detections were clarified, the nature of KL-6 mucin is not yet clearly known. Alteration in expression or glycoform of KL-6 mucin is suggested to influence the invasive and adhesive ability of cancer cells. To clarify the characteristics and biological functions of KL-6 mucin in cancer disease, the clinical applications and study of this antigen is expected to be expanded.