The occurrence of clonal chromosome aberrations in short-term cultures from synovia, osteophytes, and cartilage from patients with osteoarthritis (OA) was recently reported. Among these aberrations, a recurrent involvement of chromosome bands 12q13-15 in structural rearrangements was detected in both synovia and osteophytes. Chromosomal abnormalities of 12q13-15 are frequent among malignant and benign mesenchymal tumors, and it was recently demonstrated that the molecular target in these neoplasms is the HMGIC gene. In this study, we show by fluorescence in situ hybridization that HMGIC was disrupted by rearrangements of 12q15 in synovia from two patients with OA. The finding of HMGIC rearrangement in a lesion that is not traditionally regarded as neoplastic not only widens the spectrum of disorders that may be associated with altered function of this gene, but also provides further support for the notion that genetically rearranged cell populations are part of the OA process.