An Arabian mare was referred due to a 4-month history of bilateral mucopurulent nasal discharge, which was unresponsive to multiple courses of antimicrobials and intravenous sodium iodide. Digital radiographs revealed multiple variably sized nodular opacities within the nasopharynx. Upper airway endoscopy showed multiple, ulcerated granulomatous masses originating from the walls of the nasopharynx. Repeat culture of the exudate and from endoscopic biopsies grew only a mixed bacterial population. Standing endoscopic guided laser excision of two granulomas was performed and histopathology and culture from the center of a surgically excised granuloma identified Cryptococcus terrestris. Treatment with fluconazole (14 mg/kg bwt per os once then 5 mg/kg bwt per os q. 12 h) was administered for a total of 11 weeks. Follow-up endoscopic examination was used to guide therapy duration, and the horse has since returned to competition and remained free of infection for >1.5 years. Establishing a diagnosis of cryptococcal infection was difficult in this horse despite multiple culture attempts. This is the first report of Cryptococcus terrestris infection in a horse and treatment with oral fluconazole after surgical de-bulking was successful.