Tuberous sclerosis (TS) is an autosomal dominant hamartiosis and hamartomatosis with variable expression that is commonly associated with medically intractable seizures. Patients with TS complex (TSC) frequently have multiple brain lesions that can give rise to seizure activity. We report 9 patients with TSC who underwent epilepsy surgery at the Mayo Clinic between 1986 and 1990. Surgical procedures performed included cortical resection (n = 2) and stereotaxic lesionectomy (n = 7). Neuropathologic diagnoses were cortical tubers (n = 7) and glioneural hamartomas (n = 2). Three of 9 patients had multifocal interictal scalp epileptiform EEG activity; however, ictal recordings identified the focus of seizure activity, which in all cases corresponded to a prominent neuroimaging abnormality. Our patients have been followed for 10-72 months (mean 35 months). Four patients are seizure-free with medication, 2 are seizure-free without medication, 2 had > 80% reduction in seizure frequency, and 1 experienced only an initial temporary reduction in seizure frequency. Postoperative EEG recordings showed absence of epileptiform abnormalities in the 5 patients who are seizure-free; the other 4 patients continue to have multifocal abnormalities. These data suggest that epilepsy surgery may be beneficial in selected patients with TSC despite multifocal EEG and neuroimaging abnormalities.