Background: Cerebral blastomycosis is a rarely reported disease, and in the absence of associated, underlying systemic infection, poses a great diagnostic difficulty. Magnetic resonance imaging can sometimes provide equivocal information when trying to pinpoint a diagnosis. Classically, cerebral blastomycosis has been treated with amphotericin B. Voriconazole is a newer triazole antifungal with potential as a follow-up treatment of blastomycosis of the central nervous system after initial therapy with amphotericin B. Case Description : We describe one such case of a cerebral blastomycotic abscess, presenting in the absence of any systemic disease, which was initially thought to be a neoplasm. It was successfully treated by surgical resection followed by sequential amphotericin B and voriconazole. The patient did well with voriconazole therapy and was followed for voriconazole tolerance with liver function tests, which continued to be stable at 8 months past the initiation of therapy. At 12 months postoperatively, the patient was doing well and showed gradual improvement in a visual field cut, with no sign of recurrent infection. Conclusions: Isolated cerebral blastomycosis can present a diagnostic challenge. In the absence of systemic infection, surgical resection followed by antifungal therapy is a logical treatment plan.