Previous studies suggest a localized activation of specific areas in healthy subjects during mental calculation. We report the case of patient affected by calculation-induced seizures that were refractory to medications. We showed the cortical activation by using a functional magnetic resonance imaging (fMRI) while he was performing an arithmetic task and illustrated that, in this case, the areas commonly activated included the premotor and supplementary motor areas of both hemispheres. Furthermore, the patient showed a more significant activation of posterior parietal and prefrontal cortices after arithmetic tasks if compared to normal controls. To our knowledge, this is the first fMRI study in calculation-induced seizures, even if limited to a single patient. The potential benefits of non-conventional neuroimaging technology, such as fMRI, for understanding calculation, however, are only beginning to be tapped.