To determine the most optimal treatment of cancer patients, it is fundamental to classify human carcinomas according to their primary anatomical site of origin. As for some patients, it is difficult to identify cancers occurring at obscure location and overlapping adjacent sites. The aim of this study is to partition the primary site of 486 patients in cancers of the digestive system by the expression pattern of the mucins and cytokeratins typifying each site. The expressions of MUC1, MUC2, MUC5AC, MUC6, CK7, CK8, CK13, CK14, CK18, CK19 and CK20 were evaluated immunohistochemically in 426 adenocarcinomas and 60 hepatocellular carcinomas using the tissue-array method. The finding of MUC series showed their characteristics in case of MUC2 in the appendix cancer and MUC1 and 5AC in pancreas cancer. As for CKs 7, 13, and 19, and 20 had a feature in cancers of common bile duct, liver, and appendix, respectively. We classified cancers in 11 sites by characteristic expression of antibodies. The sensitivity, specificity, positive predictive value, and diagnostic efficacy of significant antibodies were calculated with deducing the dichotomous tree made by SPSS 10.0. Six of 11 antibodies, CK 7, CK13, CK19, CK20, MUC1, and MUC5AC distinguished 6 groups from 11 sites. We also executed the clustering of cancers to investigate total relationship among cancers. They fell into three categories, which corresponded to embryologic origin. Unlike other sites, the small intestine and colorectum cancers expressed significantly different patterns to their sublocations. Mucins and CKs showed expression patterns to classify the primary sites of digestive cancers and may be helpful in predicting the primary sites of digestive cancers.