The study of microsatellite instability (MSI) in cases of severe chronic cholecystitis and gallbladder carcinomas, to cast light on its significance for tumorigenesis, revealed MSI in 9 (30%) of 30 cases of cholecystitis and 7 (41%) of 17 carcinomas, respectively. In addition, 5 (33%) of 15 samples of background mucosa of carcinoma were positive. Respective figures for loss of heterozygosity were 3 (10%) of 30 cases of cholecystitis, 6 (35%) of 17 carcinomas, and 1 (7%) of 15 samples of adjacent nonneoplastic mucosa. No correlation was observed among MSI state, immunohistochemical hMLH1 or hMSH2 expression, and any clinicopathologic factors. MSI was observed not only in gallbladder tumors but also in severe chronic cholecystitis and background mucosa, suggesting that it may have an important role in early-stage gallbladder carcinogenesis.