The objective of this study was to determine the validity of interictal spike (IIS) source localization in frontal lobe epilepsies (FLE) using stereoelectroencephalography as a validating method. Ten patients with drug-resistant FLE were studied with high-resolution EEG and stereoelectroencephalography. Sixty-four scalp channels, a realistic head model, and different algorithms were used. For each patient, the intracerebral interictal distribution was studied and classified into one of three groups: lateral, medial, and mixed (latero-medio-basal). Surface IIS were abundant or subcontinuous for 8 of 10 FLE patients. In lateral and medial groups, intracerebral interictal activities were accurately localized. In the mixed group, source localizations designated a part of the intracerebral interictal distribution. A high degree of source localization accuracy is obtained in FLE. False-positive results were never obtained, but the extent of interictal activity could be underestimated by source localization results. Geometrical and cytoarchitectonic characteristics of the generator appear crucial to explain why medial frontal IIS (anterior para-cingulate gyrus and anterior cingulate gyrus) may be localizable whereas only the lateral orbitofrontal IIS seems to be localizable.