Surgically removing a focus of epileptogenicity attributable to a multiple sclerosis (MS) plaque has not previously been considered a treatment option. Medically intractable partial epilepsy due to a chronically situated MS plaque is uncommon because most cases are self-limiting or managed with antiepileptic medication. We report a case of partial epilepsy resulting from such a plaque situated at the gray-white interface in the anterior parahippocampal gyrus. A favorable outcome was achieved by resection of the epileptogenic area.