This case emphasizes that aggressive neurosurgical management may benefit patients with disseminated coccidioidomycosis and skull abscesses. Disseminated infection due to Coccidioides immitis, the causative agent of coccidioidomycosis, is difficult to treat and often requires prolonged antifungal therapy in addition to surgical debridement. We present a case of a young woman with disseminated coccidioidomycosis who had multiple skull lesions, two of which penetrated the skull and invaded the subgaleal and epidural spaces. Despite prolonged aggressive medical management, these lesions failed to resolve until they were surgically drained.