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Recently various authors described a new mechanism involved in the genesis of some tumors, which is characterized by a tendency for replication mistakes and by genomic instability of microsatellite repeats. This instability can be revealed through the shift in the electrophoretic mobility of the analyzed fragments, which is due to a different number of repeat units. This phenomenon is widely documented in colorectal tumors of patients affected by hereditary nonpolyposis colorectal carcinoma (HNPCC). We performed a cytogenetic and molecular study of 23 endometrial adenocarcinomas to investigate the presence of genomic instability and to evaluate the possibility of a positive correlation with specific chromosomal changes. The study of genomic instability was performed using 23 microsatellites localized over 8 chromosomes. Genomic instability of microsatellites was observed in 3 cases over all 8 analyzed chromosomes. The tumoral stage of cases with microsatellite instability does not differ significantly from the remaining tumors. As a matter of fact several cases showing no evidence of instability were more advanced (II B, III A) than tumors with instability. In ten cases we observed trisomy of chromosome 10, in some as a sole anomaly. The 3 cases with genomic instability revealed a near-diploid karyotype and all showed the presence of a supernumerary marker derived from chromosome 1 rearrangements. A derivative chromosome 1 was revealed in 4 cases without evidence of microsatellite instability. It should be noted that the presence of many unidentified markers and the small number of tumors with instability do not allow us to give a definitive significance to this observation. Our results indicate that there is not an apparent correlation between microsatellite instability and specific chromosomal abnormalities. Moreover, we did not find any correlation between pathological characteristics of the tumor and genomic instability. Microsatellite instability appears to be a relatively rare event in endometrial carcinoma.