Coccidioidomycosis involving the lung is common in endemic areas. However, it is unusual for it to present as a solitary bone lesion. Two cases of Coccidioides immitis osteomyelitis clinically and radiographically mimicked a primary bone tumor. Fine needle aspiration (FNA) biopsy of these lytic bone lesions yielded diagnostic material. Aspirated material in 1 case showed a suppurative, granulomatous inflammation and scattered spherules with refractile walls, some containing endospores consistent with coccidioidomycosis. Smears in the other case showed acute inflammation and necrosis, and rare spherules were identified with the Gomori-mathenamine-silver stain. C immitis infection was confirmed by culture in both cases. Although rare, coccidioidomycosis can involve the bone and mimic a primary bone tumor. FNA biopsy is helpful in differentiating between inflammatory and neoplastic processes involving bone by acquiring material for cytologic studies and cultures.