Prostaglandin E2 (PGE2) is related to carcinogenesis. Cyclooxygenase (COX) and prostaglandin E synthase (PGES) are involved in PGE2 synthesis. However, overall situation of COX and microsomal PGES (mPGES) expression in gastric cancer has not been studied in detail. The expression of COX and mPGES was evaluated in 45 cases of gastric cancer (22 intestinal type and 23 diffuse type), 13 gastric dysplasia, 15 intestinal metaplasia, 18 Helicobacter pylori associated gastritis, and 10 normal gastric tissues by performing immunohistochemistry and Western blot analysis. COX-1 expression was higher in intestinal type cancers than diffuse ones. COX-2 and mPGES-1 were expressed more in cancers than in paired nonneoplastic adjacent tissues, and intestinal type cancers showed higher expression of COX-2 than diffuse ones. The expression of COX and mPGES was gradually increased with progression of gastric lesions and the highest in dysplasia. mPGES-1 was expressed not only in epithelial cells but also in stromal cells, whose phenotype was myofibroblast, endothelial cells and others. In conclusion, proteins related to PGE2 biosynthesis affect both histogenesis and the carcinogenesis of human gastric cancer.