Uterine leiomyomata are thought to be monoclonal tumors; however, the factors involved in the neoplastic proliferation of uterine leiomyomata are unknown. The purpose of the present study was to characterize uterine leiomyomata using cytogenetic techniques. Thirteen leiomyoma specimens were obtained by hysterectomy or myomectomy. Short-term cultures were successfully established for all specimens, and metaphase spreads were prepared by conventional techniques. Clonal chromosome rearrangements were detected in seven leiomyoma specimens (54%). These rearrangements involved chromosome bands 12q14-15 in five specimens, including three tumors with a specific translocation, t(12;14)(q14-15;q23-24). Chromosome rearrangements involving chromosome band 7q22 were identified in two specimens. A normal 46,XX karyotype was observed in six specimens. Myometrial specimens from two patients with abnormal leiomyoma karyotypes were normal cytogenetically. These results suggest that spontaneous chromosome rearrangements may be responsible for the initiation and proliferation of leiomyoma growth.