Abstract Balamuthia mandrillaris meningoencephalitis is a rare but often fatal infection; only 2 survivors have been reported to date worldwide. We report the case of an apparently immunocompetent patient (72-year-old woman) who developed several episodes of seizures without prior history of respiratory or skin infections. Magnetic resonance imaging with contrast revealed 2 ring-enhancing lesions, one in the right precentral region and the other in the left posterotemporal region. Open biopsy revealed Balamuthia encephalitis. The patient was treated with combination antibiotics (pentamidine, 300 mg intravenously once a day; sulfadiazine, 1.5 g 4 times a day; fluconazole, 400 mg once a day; and clarithromycin, 500 mg 3 times a day) and was discharged home. There have been no significant neurological sequelae at this writing (6 months after biopsy). We present this case with unusual clinical course to raise awareness of this infectious disease, which may have a more favorable outcome if diagnosed and treated in its early states.