Multiple signal classification is an alternative to the traditional dipole fitting source analysis methods. Our aim was to assess the clinical usefulness of this algorithm and to compare the localization of the epileptiform electroencephalography discharges with the regions of altered cerebral blood flow in 10 patients with complex partial seizures undergoing preoperative investigation. We performed multiple signal classification analysis of ictal and interictal discharges, and registered single-photon emission computed tomography. Localization of the ictal, but not the interictal discharges, as determined by multiple signal classification analysis was consistent with the regions showing perfusion changes on the single-photon emission computed tomography. Multiple signal classification analysis is a promising tool in localizing foci in patients with complex partial seizures and may contribute to the preoperative evaluation.