Primary synovial chondromatosis is a proliferation of cartilaginous bodies within the synovial membrane, bursa, or tendon sheath. Historically, it has been characterized as a rare, monoarticular, benign arthropathy of uncertain etiology, typically involving a single large joint in a young adult. Males are affected more commonly than females1. The knee is involved most frequently, followed by the hip, elbow, shoulder, ankle, and wrist2-4; however, smaller joint involvement, including that of the spine, foot, and hand, has been reported5-8, as has involvement of the acromioclavicular, temporomandibular, and sternoclavicular joints9-12. The Massachusetts General Hospital tumor database contains eighty-six recorded cases of synovial chondromatosis; these cases include involvement of the knee (thirty-three cases), the hip (sixteen cases), the shoulder (eight cases), the ankle (seven cases), the foot (seven cases), the elbow (five cases), and miscellaneous locations (ten cases). Malignant degeneration of synovial chondromatosis into chondrosarcoma is a described, but extremely rare, event. We describe a unique case of synovial chondromatosis in the shoulder, which, following multiple recurrences with a repeatedly benign histologic appearance but abnormal results on deoxyribonucleic acid (DNA) flow cytometry, ultimately demonstrated histologic evidence of malignant transformation. The aneuploid DNA of this specimen distinguishes it from all other cases of synovial chondromatosis in the Massachusetts General Hospital tumor database. Our patient was informed that data concerning the case would be submitted for publication. A forty-seven-year-old man presented in February of 1999 with a two-year history of right shoulder pain and generalized shoulder discomfort that was most frequently related to activity. In addition, the patient reported that lying on the shoulder at night caused pain. The patient had not experienced trauma or any other inciting event, nor did he have any motor or sensory deficits or any additional …