The incidence of headache at the onset of relapsing-remitting pediatric multiple sclerosis (MS) is more frequent than in the adult MS population, but headache as the only symptom of a relapse, both in adults and children, is unusual. Here we describe the case of a 5-year-old child who developed MS and in whom migraine-like headache was the presenting symptom at both the onset of the disease and the following 2 relapses. Moreover, the first relapse was characterized by the occurrence of headache that fulfilled the time criteria for status migrainosus. The presence of headache during MS might depend on the anatomic distribution of lesions. In our case, the demyelinating plaques localized in the midbrain, the periaqueductal gray matter, and the upper cervical cord together with the meningeal reaction and the diffuse brain swelling might have caused the onset of migraine-like headache and the status migrainosus. The causal relationship between headache and MS attacks, in our case, was also confirmed by the improvement of headache under immunomodulatory treatment for MS, because it is known that headache is often caused or exacerbated by interferon beta therapy.