Despite meticulous preoperative assessment, about 30% of patients with refractory partial epilepsy due to hippocampal sclerosis fail to become seizure free after appropriate temporal lobe surgery. Perioperative complications, hippocampal remnants, and bitemporal disease do not account for all failures; extrahippocampal epileptogenic tissue must persist in some patients. Such dual pathology is detected on routine visual inspection of magnetic resonance images in about 15% of patients with hippocampal sclerosis, but most such patients are excluded from surgery. We postulated that some patients have occult extrahippocampal cerebral structural abnormalities (i.e., subtle dual pathology) and that the presence of these abnormalities would be associated with a poor surgical outcome. Quantitative postprocessing of preoperative magnetic resonance images from 27 patients subsequently proved to have hippocampal sclerosis demonstrated extrahippocampal structural abnormalities in 14, 10 of whom did not become seizure free, while 11 of 13 patients without such changes did become seizure free (chi2, p < 0.005). Such structural information may supplement clinical decision making in some patients being evaluated for epilepsy surgery and help to explain the biological basis of poor outcome from such surgery.