To evaluate morphometric analysis program (MAP) and quantitative positron emission tomography (QPET) in epileptogenic zone (EZ) identification using a simultaneous positron emission tomography/magnetic resonance imaging (PET/MRI) system in MRI-negative epilepsies.Seventy-one localization-related MRI-negative epilepsies who underwent preoperative simultaneous PET/MRI examination and surgical resection were enrolled retrospectively. MAP was performed on a T1-weighted volumetric sequence, and QPET was analyzed using statistical parametric mapping (SPM) with comparison to age- and gender-matched normal controls. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of MAP, QPET, MAP + QPET, and MAP/QPET in EZ localization were assessed. The correlations between surgical outcome and modalities concordant with cortical resection were analyzed.Forty-five (63.4%) patients had Engel I seizure outcomes. The sensitivity, specificity, PPV, and NPV of MAP were 64.4%, 69.2%, 78.3%, and 52.9%, respectively. The sensitivity, specificity, PPV, NPV of QPET were 73.3%, 65.4%, 78.6%, and 58.6%, respectively. MAP + QPET, defined as two tests concordant with cortical resection, had reduced sensitivity (53.3%) but increased specificity (88.5%) relative to individual tests. MAP/QPET, defined as one or both tests concordant with cortical resection, had increased sensitivity (86.7%) but reduced specificity (46.2%) relative to individual tests. The regions determined by MAP, QPET, MAP + QPET, or MAP/QPET concordant with cortical resection were significantly associated with the seizure-free outcome.QPET has a superior sensitivity than MAP, while the combined MAP + QPET obtained from a simultaneous PET/MRI scanner may improve the specificity of the diagnostic tests in EZ localization coupled with the preferable surgical outcome in MRI-negative epilepsies.© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.