Hepatocyte nuclear factor 4alpha (HNF4alpha) isoforms in the human stomach have not been fully investigated. The purpose of the present study was to evaluate the expression of P1 and P2 promoter-driven HNF4alpha (P1 and P2-HNF4alpha) in differentiated-type early gastric carcinomas (DEGC). P1- and P2-HNF4alpha expression was examined immunohistochemically both in non-neoplastic mucosa and carcinoma from surgical specimens. In all samples of non-neoplastic mucosa, foveolar, cardiac, fundic and pyloric gland epithelium was negative for P1-HNF4alpha, but was positive for P2-HNF4alpha. Intestinal metaplasia was positive for P1 and P2-HNF4alpha in all cases. Gastric carcinomas were classified into four mucin phenotypes based on the pattern of mucin expression: gastric, intestinal, mixed and null type. DEGC showed striking differences in the staining pattern for P1-HNF4alpha according to the mucin phenotype. Gastric carcinomas of intestinal, mixed and null type showed high positivity for P1-HNF4alpha, but the gastric type was negative for P1-HNF4alpha in all but one tumor. In contrast, P2-HNF4alpha was expressed in all tumors regardless of the mucin phenotype. Negative expression of P1-HNF4alpha was indicated as one of the useful immunohistochemical markers in the classification of mucin phenotype of both non-neoplastic mucosa and cancers of gastric phenotype.