To determine whether the clinical features of tonic seizures (TSZ) are useful for lateralization of epileptic syndromes and the differential diagnosis of focal epileptic syndromes. From a group of 481 patients, 123 patients with TSZ (44 females; mean age, 22.9 years; mean age at onset, 7 years; mean duration of epilepsy, 16 years) were selected. A total of 1595 epileptic seizures, documented during videoelectroencephalographic monitoring, were analyzed. Patients who had had surgery for epilepsy previously were excluded. Seizures were classified using a semiological seizure classification. Epilepsy syndromes were classified using all test data (electroencephalography, magnetic resonance imaging, computed tomography, positron emission tomography, and single-photon emission tomography). Data were compared using chi2 analysis or the Fisher exact test. More patients with TSZ had extratemporal than temporal lobe epilepsies (79% vs. 1.7%; p < 0.0001) among those with an epilepsy localized to one lobe (n = 306). In the 123 patients, TSZ were part of 170 different seizure evolutions. Seizure evolutions began with TSZ as the first seizure type more often in patients with frontal lobe epilepsy (FLE) compared with patients with parieto-occipital lobe epilepsy (POLE) (40% in POLE vs. 67% in FLE; p < 0.05). In contrast, TSZ in POLE were more likely to be preceded by auras (50% in POLE vs. 26% in FLE; p < 0.05). TSZ were bilateral in 129 (76%) and unilateral in 41 (24%) seizure evolutions. Unilateral TSZ correctly lateralized the epilepsy syndrome to the contralateral hemisphere. Analysis of seizure semiology and evolution in patients with TSZ is helpful for differentiating between focal epilepsies of temporal, frontal, and parieto-occipital origin. Unilateral TSZ provide useful information for the lateralization of the epileptic syndrome.