The aim of our study was to explore restless legs syndrome (RLS) frequency in multiple sclerosis (MS)-patients and establish whether RLS could be a symptom of MS. Over a period of 1 year, we consecutively enrolled 202 MS-patients and 212 healthy controls, matched for sex and age, in a case-control study. All of them filled in a structured questionnaire according to IRLSSG criteria. Those patients who fit the diagnostic criteria were subsequently examined by a neurologist to verify the effective presence of RLS. A total of 91 MS-patients (45%) responded positively to the questionnaires. The diagnosis of RLS was carried out in 29 subjects (14.4%). Among the healthy controls, a definite diagnosis of RLS was achieved only in 6 subjects (2.8%). The risk of MS patients to present RLS was significantly higher (OR.5.76 P:0.00002) than the general population. None of them was affected by other medical conditions related to RLS developing. The 62 remaining patients presented numbness and weakness of the legs not suggestive of RLS. Our findings confirm a significant correlation between MS and RLS. In our opinion, MS must be definitively included among RLS causes.