Cytogenetic analysis of short-term cultures from two uterine leiomyomas revealed, in addition to the primary abnormality, the reciprocal translocation t(12;14)(q14-15;q23-24), secondary structural changes that in both cases included ring chromosomes and rearrangements of chromosome 1. One tumor had the karyotype 46,XX,r(1)(p34q32),ins(8;9)(q13;q13q22),t(12;14)(q14-15;q23- 24). Massive numerical rearrangements were found in the second leiomyoma, with chromosome numbers ranging from 47 to 92. In spite of this variability, two main cell populations could be discerned, one near-diploid, the other hypotetraploid, with most mitoses having chromosome numbers between 80 and 88. These findings were corroborated by flow cytometry, which revealed two peaks corresponding to DNA indexes of 0.97 and 1.77. The structural abnormalities t(1;1)(p31;q44) and t(12;14)(q14-15;q23-24) were present in all karyotypically abnormal cells, and one or more unidentified ring chromosomes were observed in most of the hypotetraploid mitoses. In no cells were double copies of the t(1;1) and t(12;14) rearrangements detected. The similarity between the secondary changes in the cases reported here suggests that clonal evolution in uterine leiomyoma is nonrandom.