In refractory epilepsy, the goal of neuroimaging is to localize the region of seizure onset. Tracers that accumulate and remain fixed proportional to regional cerebral blood flow (rCBF) at the time of injection are used to obtain SPECT images of the brain activity during and between seizures. The most used technique for detecting the epileptogenic zone (EZ) is to threshold the co-registered and normalized subtraction of these two images. This method has proven to be very useful but has some disadvantages: result depends on the selected threshold and abundance of false detections. In this paper we propose an a-contrario algorithm for detecting regions of the brain with significant changes in the rCBF using two SPECT images. This new method arises from formal deduction and no arbitrary parameters are involved. Comparisons of both methodologies on six patients are presented. The proposed algorithm shows good results in all cases and is more robust than the thresholding method.