Mild encephalitis with reversible lesion in the splenium is a clinicoradiological syndrome characterized by a variegated symptomatology with a solitary mass in the central portion of the splenium of the corpus callosum. Complete spontaneous resolution is the hallmark of this syndrome, though its pathogenesis is still unknown. We describe the clinical picture of a 51-year-old woman who developed a partial sensitive seizure, with MRI evidence of a lesion localized in the posterior portion of the corpus callosum. The patient made a full recovery thanks to the administration of antiepileptic drugs. Acquiring knowledge of this syndrome, in the wide diagnostic panel which includes vertebrobasilar diseases besides the broad range of metabolic and electrolyte disorders, is crucial to a prompt clinical diagnosis and in establishing a reliable prognosis at an early stage.