We report two cases of musculoskeletal syndrome (myalgia, arthralgia, arthritis, hyperostosis) that developed in male adolescents who had severe acne (acne conglobata and acne fulminans). In both patients the hyperostosis of the right clavicle aroused the suspicion of a bone tumor or osteomyelitis, which was excluded by histologic examination. Radiologic and laboratory characteristics of musculoskeletal syndrome associated with acne conglobata and acne fulminans are reviewed as well as isotretinoin therapy. The problems of differential diagnosis are also discussed.