TCF1: (transcription factor 1) encoding hepatocyte nuclear factor 1alpha (HNF1alpha) is mutated in 50% of liver cell adenomas, a benign tumor closely associated with oral contraceptive use. These genetic alterations inactivate both alleles, leading to the absence of wild-type HNF1alpha expression in liver cell adenomas. To search for a role of HNF1alpha in other hormone-related neoplasias, we screened for HNF1alpha mutations in a series of 36 endometrial carcinomas, 29 breast carcinomas and 20 ovarian epithelial tumors. HNF1alpha mutations were identified in 4/36 (11%) of endometrial tumors. No mutation was found in ovarian and breast tumors. HNF1alpha mutations were somatic in all cases, monoallelic in three cases and biallelic in one case. These results suggest that HNF1alpha may contribute to endometrial carcinogenesis through complete HNF1alpha inactivation like in liver cell adenoma or by haploinsufficiency like in MSI-H colorectal cancer.