Expression of mucin core protein of mammary type (MUC-1 core protein) was investigated in primary hepatic carcinoma (25 cases of cholangiocarcinoma, 15 cases of combined hepatocellular-cholangiocellular carcinoma and 18 cases of hepatocellular carcinoma) with monoclonal antibody DF3 and a standard avidinbiotin complex method. MUC-1 core protein was almost always expressed in cholangiocarcinoma and in the cholangiocarcinoma area of hepatocellular-cholangiocellular carcinoma to a varied degree, whereas such expression was virtually absent in hepatocellular carcinoma and the hepatocellular carcinoma areas of hepatocellular-cholangiocellular carcinoma. Nonneoplastic intrahepatic biliary epithelium, as well as hepatocytes, was virtually negative for this protein. In well-differentiated cholangiocarcinoma, this protein tended to be expressed on luminal surfaces, whereas poorly differentiated cholangiocarcinoma showed cell membranous or diffuse cytoplasmic staining patterns. Double staining with Alcian blue (pH 2.5) and immunostaining for MUC-1 core protein showed that although some parts of cancerous areas were positive for both stains, most cancerous areas were only positive for one. Alcian blue—positive areas were dominant over MUC-1 core protein—expressing areas in well-differentiated cholangiocarcinoma, whereas the reverse was the case in poorly differentiated cholangiocarcinomas and also in cholangiocarcinoma areas of hepatocellular-cholangiocellular carcinoma. This study is the first report to document that cholangiocarcinoma and cholangiocarcinoma areas of hepatocellular-cholangiocellular carcinoma express MUC-1 core protein. In addition, MUC-1 core protein—expressing areas and Alcian blue—positive areas in cholangiocarcinoma and cholangiocarcinoma areas of hepatocellular-cholangiocellular carcinoma were reciprocally distributed in most cancerous areas, suggesting that immunostaining for MUC-1 core protein can be used to supplement conventional mucin histochemical study in cholangiocarcinoma and hepatocellular-cholangiocellular carcinoma. (Hepatology 1994;20:1192–1197).