A case of septic arthritis from coccidioidomycosis in a 62-year-old man is described. The diagnosis was made by fine-needle aspiration and supported by positive cultures and exoantigen testing. Coccidioidomycosis can infect bones and joints, especially the knee. This case is presented to increase awareness of involvement of the knee by this organism, and to demonstrate the feasibility of diagnosis by fine-needle aspiration. The cytologic findings of coccidioidomycosis of the knee are described and discussed.