Three hundred forty-eight patients with solitary pulmonary nodules underwent needle biopsy of the lung in an endemic area for coccidioidomycosis. The purposes of the study were to establish the value of smears and cultures from needle biopsy specimens in the diagnosis of solitary coccidioidal granuloma and to determine how the final diagnosis was established for patients without a clear-cut diagnosis after initial biopsy. Spherules of Coccidioides immitis were initially identified in 49 of the 96 patients with coccidioidomas. Only three of 35 cultures from biopsy-proved coccidioidal lesions were positive (8.6% yield); nevertheless, cultures were cost-effective in nondiagnostic cases. Thoracotomy should be delayed until the results of cultures are known if findings of skin tests, serologic studies, and roentgenography make a benign diagnosis plausible.