Cryptococcus neoformans is an uncommon but treatable cause of osteomyelitis that affects both normal and immunocompromised hosts. When not considered as a diagnostic possibility, C. neoformans infection may result in increased morbidity. The spectrum of disease at presentation extends from an asymptomatic patient with an osteolytic lesion on radiograph to a patient with signs and symptoms of systemic disease. Once diagnosis has been established (often by closed aspiration), optimal therapy appears to involve a combination of amphotericin B, flucytosine, and surgical debridement.