Pyomyositis is an uncommon condition that may present a difficult problem in diagnosis. We report the development ofStreptococcus pneumoniaepyomyositis involving the iliacus, iliopsoas, and gluteus muscles in a patient with elevated serum levels of antinuclear and antiphospholipid antibodies but without clinical evidence of connective tissue disease. Magnetic resonance imaging demonstrated rapid evolution of the infection, with progression from muscle edema to abscess formation over a period of 10 days. The diagnosis was initially missed, and osteomyelitis and sacroiliitis developed. Pyomyositis should be suspected in patients with the acute onset of severe, localized muscle pain and fever. As in this case, failure to promptly diagnose and treat this infection can result in significant morbidity.