Cytogenetic evidence of clonal evolution was detected in five uterine leiomyomas. In two tumors, two clones were found, the third tumor had four, the fourth had nine, and the fifth had I 2 clones. The first tumor had trisomy I 2 as the primary anomaly and a sideline that also contained a de1(7)(q2 I q3 I ). Both clones of the second tumor had three structural changes in common but differed by the presence in the more advanced clone of an inv(7)(q31q34). Two cytogenetically unrelated pairs of clones were seen in the third tumor: One clone had a stemline of 46 and an r( I); a sideline had developed through duplication of this clone. The other pair had a de1(7)(q2 I q3 I) in common. The last two tumors both had t( 12; I4)(q 14-1 5;q2&24) as the primary abnormality. They also had a high frequency of telomeric associations that involved certain chromosome arms only. One of the secondary changes in the fourth tumor was a de1(7)(q21q31); the principal secondary change in the fifth case was a ring chromosome I of variable size in the different clones. The analysis of these five uterine leiomyomas and the collation of the results with previously obtained data lead us t o conclude that de1(7)(q2 I q3 I) is secondary t o t( 12; 14) and + I 2 in this tumor type, and that ring formation invoking chromosome I material, often with duplication of segments, is a common phenomenon during clonal evolution. The fact that the tumors were classified as cellular and had an increased mitotic rate indicates a parallel development between histologically detectable tumor progression and cytogenetically recognizable clonal evolution in uterine leiomyomas.