The aim was to investigate the lifetime prevalence of headache and primary headache (diagnoses according to International Headache Society criteria) in multiple sclerosis (MS). The relationships between headache and clinical features of MS and MS therapy were also investigated. We studied 137 patients with clinically definite MS; 88 reported headache, 21 of whom developed headache after the initiation of interferon. The prevalence of all headaches in the remaining 116 patients was 57.7%. Migraine was found in 25.0%, tension-type headache in 31.9%, and cluster headache in one patient. A significant correlation (P = 0.007, Fisher's exact test) between migraine and relapsing-remitting MS was found. Primary headaches are common in MS patients. Further studies are needed to clarify the mechanisms underlying this association, particularly the association between migraine and relapsing-remitting MS, and the role of interferon in the development of new headache.