Microsatellite instability (MI) has been observed in endometrioid adenocarcinomas of the endometrium, either arising sporadically or in association with the hereditary colon cancer syndrome. Genes known to contain mononucleotide short tracts in their coding sequence are regarded as targets for mutations in these tumors. BAX is a proapoptotic gene that contains a tract of eight consecutive deoxyguanosines in its third coding exon. DNA of 26 patients with endometrial carcinoma was extracted from blood and from fresh-frozen and paraffin-embedded tumor tissue. For MI analysis, microsatellite loci on chromosomes 3, 5, 10, 12, and 18 were amplified by PCR. Frameshift mutations in the (G)8 tract of BAX were detected by single-strand conformation polymorphism (SSCP) analysis. MI at three or more loci was detected in 13 cases. BAX frameshift mutations were detected in seven MI+ tumors (53.8%), but in none of the 13 MI- neoplasms. In two cases, identical BAX frameshift mutations were detected in different areas of the neoplasm, whereas in the other five cases, BAX mutations were heterogeneously distributed throughout the tumor. Immunostaining with antibodies against the carboxy terminus of BAX protein was very useful in assessing the heterogeneous distribution of BAX frameshift mutations in the neoplasms. The results suggest that BAX frameshift mutations are frequent in endometrial carcinomas with MI, probably playing a role in the process of tumor progression of these neoplasms.