OBJECTIVE: One barrier hindering high frequency brain signals (HFBS, >80 Hz) from wide clinical applications is that the brain generates both pathological and physiological HFBS. This study was to find specific biomarkers for localizing epileptogenic zones (EZs). METHODS: Twenty three children with drug-resistant epilepsy and age/sex matched healthy controls were studied with magnetoencephalography (MEG). High frequency oscillations (HFOs, > 4 oscillatory waveforms) and high frequency spikes (HFSs, > 1 spiky or sharp waveforms) in 80-250 Hz and 250-600 Hz bands were blindly detected with an artificial intelligence method and validated with visual inspection. The magnitude of HFOs and HFSs were quantified with spectral analyses. Sources of HFSs and HFOs were localized and compared with clinical EZs determined by invasive recordings and surgical outcomes. RESULTS: HFOs in 80-250 Hz and 250-600 Hz were identified in both epilepsy patients (18/23, 12/23, respectively) and healthy controls (6/23, 4/23, respectively). HFSs in 80-250 Hz and 250-600 Hz were detected in patients (16/23, 11/23, respectively) but not in healthy controls. A combination of HFOs and HFSs localized EZs for 22 (22/23, 96%) patients. CONCLUSIONS: The results indicate, for the first time, that HFSs are a newer and more specific biomarker than HFOs for localizing EZs because HFOs appeared in both epilepsy patients and healthy controls while HFSs appeared only in epilepsy patients.