Uterine leiomyomata are among the most common of human neoplasms and are associated with abnormal uterine bleeding, infertility, and abdominal pain. Uterine leiomyosarcomata are presumed to be the malignant counterpart to uterine leiomyomata and are very rare. Transformation of uterine leiomyoma (ULM) into uterine leiomyosarcoma (ULMS) is yet to be conclusively confirmed, and each type of tumor may represent a distinct genetic entity. We used comparative genomic hybridization (CGH) to evaluate DNA sequence copy-number changes in 12 specimens of ULM and 8 of ULMS. CGH analysis of ULM demonstrated chromosomal imbalances in 8 of 12 (66. 7%) specimens. The most frequent ULM gains were observed at 9q34 (a novel finding) and on chromosome 19. Other ULM imbalances included gains and losses of chromosome 1p, losses on 7q, and gains on 12q. All ULMS specimens demonstrated chromosomal aberrations. Chromosome 1 imbalances were very prominent. The most frequent losses were detected on 14q and 22q. Losses on 14q are rarely seen in other types of leiomyo-sarcoma and may be a distinctive feature of ULMS. Gains on chromosomes 8, 17, and X were observed in half the cases and were accompanied by high-level amplification. Other chromosome arms overrepresented included 12q and 19p. The absence of specific anomalies common to all ULM and ULMS argues against their being benign-malignant counterparts.