An immunocompetent patient from a nonendemic region developed a rare intramedullary thoracic histoplasmoma. A native Arizonan, with no history of travel to endemic regions, received 3 months of itraconazole for confirmed gastrointestinal histoplasmosis at an outside institution. Two years later she experienced the rapid onset of paraplegia and lost bowel and bladder function. Magnetic resonance imaging demonstrated a ring-enhancing intramedullary lesion at T2 and signal abnormality from C2 to T5. Emergent T2–T3 laminectomy was performed with ultrasonographically guided intradural exploration and midline myelotomy. The intramedullary abscess was drained. She was nonambulatory, but motor function was partially restored. An Ommaya reservoir was later placed to deliver amphotericin and a new antifungal agent, voriconazole. Magnetic resonance imaging confirmed that the infection had resolved. Intramedullary spinal histoplasmoma is a rare manifestation of disseminated histoplasmosis, particularly in nonendemic regions. Surgery for focal mass lesions and aggressive antifungal chemotherapy are the optimal treatment. Newer central nervous system-penetrating antibiotics show promise in refractory cases.