We investigated whether ictal single photon emission computed tomography (SPECT) with 99Tcm-ethyl cysteinate dimer (ECD) could differentiate between temporal (TE) and extratemporal epilepsy (ETE) in 30 consecutive patients (n = 21 for TE, n = 9 for ETE), all of whom had excellent postoperative seizure control (class I according to Engel's classification). Ictal SPECT showed isolated temporal hyperperfusion in 90% (19 out of 21) of the TE patients and normal perfusion in two patients. All the ETE patients had ictal SPECT findings consistent with extratemporal seizure onset. The sensitivity of ictal ECD-SPECT for correct localization of the seizure onset zone was 80% in all patients, 86% in TE patients and 66% in ETE patients. Although ictal ECD-SPECT has a lower sensitivity in ETE than in TE, it can be used to clearly distinguish between TE and ETE. It provides non-invasive imaging information for use in further diagnostic and treatment strategies in patients with drug-resistant focal epilepsy.