Consistent rearrangements of chromosomes 13q and 16q have been identified in spindle cell and pleomorphic lipomas by cytogenetics. Mammary-type myofibroblastoma and cellular angiofibroma show overlapping histologic features and similar chromosomal losses, suggesting a possible relationship among these tumor types. The tumor suppressor gene RB1, encoding the retinoblastoma (Rb) protein, is located at 13q14, within a minimally deleted region in spindle cell lipoma. The purpose of this study was to examine expression of Rb by immunohistochemistry in spindle cell lipoma, pleomorphic lipoma, mammary-type myofibroblastoma, and cellular angiofibroma, and in histologic mimics, to determine its potential diagnostic utility. Whole-tissue sections of 194 tumors were evaluated: 18 spindle cell lipomas, 20 pleomorphic lipomas, 19 mammary-type myofibroblastomas, 16 cellular angiofibromas, 22 conventional lipomas (8 intramuscular), 18 atypical lipomatous tumors (all positive for MDM2 and CDK4), 19 solitary fibrous tumors, 19 myxoid liposarcomas, 14 hibernomas, 11 deep (aggressive) angiomyxomas, 9 angiomyofibroblastomas, and 9 vulval fibroepithelial stromal polyps. Immunohistochemistry was performed after pressure cooker antigen retrieval using a mouse anti-Rb monoclonal antibody. Nuclear staining for Rb was scored as "intact" or "deficient." Rb expression was deficient in all spindle cell lipomas, pleomorphic lipomas, and cellular angiofibromas and in 17 (89%) mammary-type myofibroblastomas. Rb staining was sometimes difficult to interpret in cellular angiofibromas with reactive stromal changes. Rb was also deficient in 2 (9%) conventional lipomas. Rb expression was intact in all other tumor types evaluated. In summary, of the soft tissue tumors associated with 13q deletions, all spindle cell lipomas, pleomorphic lipomas, and cellular angiofibromas and most mammary-type myofibroblastomas show loss of Rb expression. Rb expression is intact in histologic mimics. These findings reinforce the pathogenetic relationship among this group of tumors and demonstrate the potential diagnostic utility of immunohistochemistry for Rb.