Solitary fibrous tumor (SFT) presenting in the pleura and other soft tissue sites and hemangiopericytoma (HPC) presenting at various soft tissue sites are mesenchymal tumors that share many histologic and immunohistochemical features. This raises the questions of whether these tumors are related and whether they belong within the spectrum of a single biologic entity. The behavior of both SFTs and HPCs is difficult to predict histologically. The genetic background of both SFTs and HPCs is poorly known, but it could be helpful in the evaluation of malignancy and could give clues to their possible relationship. In this study, we analyzed 15 SFTs and 11 HPCs by comparative genomic hybridization (CGH), a powerful molecular cytogenetic tool that can be applied to DNA extracted from formaldehyde-fixed and paraffin-embedded tissue. All of these tumors were immunohistochemically similar and showed reactivity for CD34-antigen but not for keratins, desmin, or muscle actins. Only 1 SFT smaller than 10 cm showed DNA copy number changes (a single loss in chromosome 13), but 7 of 8 SFTs larger than 10 cm (including all 4 tumors with more than 4 mitoses per 10 high power fields) showed changes, mostly chromosomal gains in 5q 7, 8, 12, and 18. Four cases showed losses, two of them in chromosome 13 and two others in 20q. These findings suggest that CGH might be useful in the evaluation of malignant transformation in SFT. The most common change, gain of the entire chromosome 8, seen in two cases as the only change, suggests trisomy 8 and parallels a similar finding previously described in other fibrous tumors, such as subsets of desmoid fibromatosis and infantile fibrosarcoma. In contrast, HPCs, including large and mitotically active tumors, showed no DNA copy number changes on CGH. This suggests that HPC is genetically different from SFT.