Uterine lipoleiomyomas are extremely rare tumors consisting of a mixture of mature adipocytes and smooth muscle cells. Using G-banding and FISH, we characterized a complex rearrangement involving chromosomes 7, 8, 10, 11, 12, and 14 in one of these tumors. The region 14q23–24 was inserted into the long arm of the derivative chromosome 12, between the 3′ end of HMGIC and 7q21–22, another region often rearranged in uterine leiomyomas. Other portions of chromosomes 12 and 14 were involved in derivative chromosomes 7, 11, 12, and 14. A chromosome 8 was involved in a three-way rearrangement including the derivative 7, a ring chromosome 10, and a small derivative chromosome 8 bearing segments of chromosomes 10 and 11. No abnormality of chromosome 5 was detected, in contrast to two previously reported cytogenetic analyses of uterine lipoleiomyoma. The consistent finding of chromosomes 12 and 14 on different derivatives indicates that the t(12;14) was a primary event. In addition, immunohistochemical studies showed that HMGI-C was aberrantly expressed in this tumor. These observations suggest that uterine lipoleiomyomas have a pathogenetic origin similar to that of typical leiomyomas. Genes Chromosomes Cancer 27:209–215, 2000. © 2000 Wiley-Liss, Inc.