Thirty-seven endometrial cancers were subjected to an allelotype analysis in an attempt to identify chromosomal regions that are lost in a significant portion of tumors and to identify tumors characterized by replication errors. Thirty-nine highly polymorphic microsatellite markers representing all chromosomal arms, excluding the X and the short arms of the acrocentrics, were examined. An average of 20 informative cases were evaluated for each marker. Genetic alterations were detected in 30 of the 37 tumors. Replication errors were identified in 8 tumor specimens. Loss of heterozygosity was observed for loci on all chromosomes examined with the exception of chromosomes 4 and 20. The two most frequent sites of loss were at the marker loci examined on 10q (40%) and 17p (29%). Six additional simple sequence repeat markers from 10q were genotyped in an effort to refine the region of 10q loss. The chromosome 10 markers used in these studies were physically mapped with the use of a panel of somatic hybrids that retain defined portions of chromosome 10. The observed patterns of loss of sequences on 10q suggest a role for a tumor suppressor gene in the 10q23-26 region in the development or progression of endometrial cancers.