Microsatellite instability (MIN) has been studied in a variety of carcinomas and gynecologic sarcomas, but never in musculoskeletal sarcomas.We evaluated 16 skeletal and soft tissue sarcomas at nine genetic loci from chromosomal regions 1q, 5q, 7q, 12p, 13q, 17p, 19q, and two at 11p--all potential regions of interest regarding musculoskeletal sarcomas.MIN was identified at one or more loci in seven of the cancers studied (44%). Three tumors had more than one locus with MIN and one tumor, a high-grade osteogenic sarcoma, had five of nine loci positive for MIN.These results indicate that musculoskeletal sarcomas show instability in areas inside and outside the loci of known oncogenes. Areas of mismatch repair, as heralded by MIN, may contribute to the vast heterogeneity of these neoplasms.