Significance Millions of people affected by epilepsy may undergo surgical resection of the epileptic tissues to stop seizures if such epileptic foci can be accurately delineated. High-frequency oscillations (HFOs), existing in electroencephalography, are highly correlated with epileptic brain, which is promising for guiding successful neurosurgery. However, it is unclear whether and how pathological HFOs can be differentiated to localize the epileptogenic tissues given the presence of various nonepileptic high-frequency activities. Here, we show morphological and source imaging evidence that pathological HFOs can be identified by the concurrence of epileptiform spikes. We describe a framework to delineate the underlying epileptogenicity using this biomarker. Our work may offer translational tools to improve treatments by noninvasively demarking pathological activities and hence epileptic foci.