Data on patients with multiple sclerosis and cranial nerve involvement as a presenting sign or a sign of disease exacerbation were retrospectively analyzed. Isolated cranial nerve involvement was present in 10.4% out of 483 patients, either as a presenting symptom (7.3%) or a symptom of disease relapse (3.1%). Trigeminal nerve was most frequently involved, followed by facial, abducens, oculomotor and cochlear nerves. Only 54% of patients had brainstem MRI lesion that could explain the symptoms. As multiple sclerosis is a disease characterized by multiple neurological symptoms, while early diagnosis and therapy are critical for the prognosis and course of the disease, the diagnosis of multiple sclerosis should be considered in young adults with cranial nerve involvement.