A 5-year-old male domestic rabbit had severe swelling of the left hindlimb. Radiographs demonstrated a proliferative, infiltrative lesion involving the stifle joint, femur and soft tissues of the thigh. Osteomyelitis or neoplasia was suspected and the limb was amputated. Grossly, there was a multilobular mass comprised of cystic spaces containing yellow mucinous material. Microscopically, the mass formed coalescing lobules of stellate to rounded cells embedded in varying amounts of myxoid to collagenous matrix, and some rimmed by narrow walls of metaplastic bone and/or cartilage, and some infiltrated by plasma cells, lymphocytes, heterophils and histiocytes. Immunohistochemically, neoplastic cells expressed vimentin but not cytokeratin, sarcomeric actin, Mac387 or BLA36. Cytokeratin was not detected in normal synovial cells. The radiographic, gross and histological findings were most consistent with synovial myxoma; however, because of the extensive involvement of the limb in the absence of confirmed metastatic disease, the term infiltrative synovial myxoma was applied.