Seventy-six gastric carcinomas were analyzed with regard to whether or how microsatellite instability was associated with the development of the carcinoma. Microsatellite instability occurred as a late genetic alteration, with an incidence significantly higher in the advanced stage (17 of 51) than in the early stage (3 of 25; P < 0.05). Chromosomal losses on 5q and 17p, detected by polymerase chain reaction-restriction fragment length polymorphism, more frequently accompanied microsatellite instability (9 of 15 and 8 of 11, respectively), compared with carcinomas which lacked instability (5 of 28 and 9 of 30, respectively; P < 0.01 and P < 0.05, respectively). Epstein-Barr virus was observed in only 8 of 76 carcinomas, none of which was associated with microsatellite instability. No significant correlation was found between instability and the familial tendency to develop gastric carcinomas. Our results suggest that microsatellite instability might play a role in the progression of gastric carcinomas but not in Epstein-Barr virus-associated gastric carcinomas.