Purpose: As mesial temporal lobe epilepsy (TLE) shows hypometabolism of medial and lateral temporal lobe, we investigated whether symmetric uptake of F-18-FDG in medial temporal lobes can differentiate mesial from lateral TLE. Materials and Methods: In 113 patients (83 mesial TLE, 30 lateral TLE) who underwent anterior temporal lobectomy and/or corticectomy with good surgical outcome, we performed F-18-FDG PET and compared F-18-FDG uptake of medial and lateral temporal lobes. All the patients with mesial TLE had hippocampal sclerosis except one congenital abnormal hippocampus. Patients with lateral TLE revealed cerebromalacia, microdysgenesis, arteriovenous malformation, old contusion, and cortical dysplasia. Results: Sensitivity of F-18-FDG PET and MR for mesial TLE was 84% (70/83) and 73% (61/83), respectively. Sensitivity of F-18-FDG PET and MR for lateral TLE was 90% (27/30) and 66% (20/30), respectively. Twelve patients were normal on F-18-FDG PET. 101 patients had hypometabotism of lateral temporal lobe. Among 88 patients who showed hypometabolism of medial temporal lobe as well as lateral temporal lobe, 70 were mesial TLE patients and 18 were lateral TLE on pathologic examination. Positive predictive value of medial temporal hypometabolism for mesial TLE was 80%. Among 13 patients who showed hypometabolism of only lateral temporal lobe, 4 were mesial TLE and 9 were lateral TLE. Positive predictive value of hypometabolism of lateral temporal lobe for the diagnosis of lateral TLE was 69% (9/13). Normal MR findings stood against medial TLE, whose negative predictive value was 66%. Conclusion: Lateral temporal lobe epilepsy should be suspected when there is decreased F-18-FDG uptake in lateral temporal lobe with normal uptake in medial temporal lobe.