Lipoma is a benign tumor composed of mature adipocytes and one of the most common mesenchymal tumors seen in adults. Rearrangement of HMGA2 in chromosome band 12q15 has been found in approximately 60-70% of ordinary lipomas with cytogenetic abnormalities. Herein, we report two novel HMGA2 fusion sequences in lipomas with chromosome 12 rearrangements. Cytogenetic studies showed 12q abnormalities in both cases, and fluorescence in situ hybridization (FISH) confirmed the involvement of HMGA2 in each instance. Rapid amplification of cDNA ends (RACE) PCR experiments revealed that one lipoma contained a fusion of the HMGA2 3' untranslated region (UTR) to a genomic area downstream of the DYRK2 locus on 12q15; the second lipoma showed a fusion of the HMGA2 3' UTR to a genomic sequence upstream of the DCN locus on 12q21. In both instances the breakpoint on HMGA2 occurred downstream to let-7 miRNA (microRNA) consensus binding site (CBS) 1. These two and several other previously reported tumors containing HMGA2 3' UTR rearrangements show breakpoints after let-7 miRNA CBS 1, which suggests that the elimination of this miRNA binding site is not critical for driving HMGA2 transcriptional upregulation.