Microsatellite instability (MI), detected as electrophoretic shifts in allele sizes of microsatellite DNA sequences, has been identified in some colorectal carcinomas. Investigators have previously attributed such microsatellite instability to replication errors (RER). The colorectal carcinomas with RER have been found to arise either sporadically or in association with the hereditary non-polyposis colorectal cancer (HNPCC) syndrome. Because endometrial carcinoma is also commonly associated with HNPCC, we studied 30 cases of endometrial carcinoma to characterize the presence of MI in these neoplasms. Seven cases (23%) showed MI. Four cases showed both Type I (large shifts) and Type II (small shifts) mutation patterns and the remaining three cases showed Type I mutations only. We conclude that MI frequently occurs in endometrial cancers and that this type of genetic alteration may be an important pathogenetic feature of this tumor type.