Single-photon emission computed tomography (SPECT) is being increasingly used in the investigation of children with epilepsy and may provide insights into congenital malformations. We analyzed the interictal 99Tc-HMPAO-SPECT in a series of seven children with developmental disorders of the neocortex, each of them representing a prototype of cerebral dysgenesis, such as lissencephaly, pachygyria, opercular dysplasia, polymicrogyria, nodular heterotopia and band heterotopia. The patients studied were selected among 22 epileptic children with neuronal migrational disorders (NMDs). Interictal SPECT hypoperfusion was observed in the area homologous to MRI findings in all the examined children. In three patients low perfusion was also present in the opposite hemisphere, probably due to functional involvement or related to an underlying microdysgenesis, not revealed by structural imaging. EEG features were in agreement with low perfusion areas, both anatomically and functionally, in all children. In one patient hypoperfusion area differed from that revealed by MRI and EEG. Ictal SPECT has been considered a useful tool for accurately locating the epileptic focus. Nevertheless, interictal brain perfusion studies, together with proton magnetic resonance spectroscopy, may play an important role in detecting anatomic substrate in developmental disorders of the neocortex.