We report on clinical and instrumental findings of a multiple sclerosis (MS) patient with sudden right trigeminal neuralgia (TN). Magnetic resonance imaging (MRI), performed at TN onset, showed enlargement of both trigeminal nerves (TrN) at the root entry zone, with gadolinium enhancement of the cisternal portion. This is the first description of clinical and MRI findings indicative of peripheral involvement of the fifth cranial nerve in a MS patient complaining of TN. Our report shows the concomitant involvement of central and peripheral myelin in MS, and adds further highlights to the question regarding peripheral nerve involvement abnormalities associated with a disease considered limited to the central nervous system (CNS).