Twenty-seven tumor samples with a diagnosis of leiomyosarcomas (LMS) were characterized by comparative genomic hybridization. The results were compared with immunohistochemical analysis of the smooth muscle profile of the tumors and expression of the RB1 gene protein. The comparative genomic hybridization profiles suggested that 7 of the 27 tumors might have been misclassified. High levels of DNA amplification were detected in 20 different small regions and recurrently involved bands 1p34, q21, 12q13-15, 17p, and 22q. Most recurrent simple gains were noted at sites such as 1p3, 1q21, 15q12-15, 16p, 17p and 17q, 19, 20q, 22q, and Xp. Significant losses of chromosome 13 were detected in 19 of the 27 tumors with a putative common region of loss in bands 13q14-21. Losses of chromosomes 1q, 2p and 2q, 4q, 9p, 10p and 10q, 11p and 11q23, and 16q were also highly recurrent. A comparative analysis between the most frequent genomic imbalances observed in this study of LMS and the genomic imbalances observed in a large proportion of malignant fibrous histiocytomas (MFH) from a previous study demonstrated that both types of tumors had similar recurrent imbalances. Although MFH were once thought to be a separate member of the soft tissue sarcoma family, our observations support the hypothesis that MFH are a morphologic modulation in the tumoral progression of other sarcomas, particularly LMS.