Increased signal on T2-weighted magnetic resonance (MR) images has been demonstrated in skeletal muscle adjacent to neoplasms. Clinical significance of this sign was evaluated by reviewing MR images of 50 patients with musculoskeletal disorders. Increased signal in adjacent muscle was present in 22 patients, including 13 of 25 with primary or secondary malignancies of the musculoskeletal system. Biopsy specimens from the affected area in 11 of these 13 patients revealed edema (n = 8) more often than tumor invasion (n = 3). Nine of 25 patients with nonneoplastic processes had increased signal intensity in skeletal muscle because of infection, myositis, or hematoma. In patients who have not undergone previous surgery or radiation therapy and are without an inflammatory mass, increased signal intensity may be a useful indicator of malignancy.