Patients with malignant multiple sclerosis (MMS) reach a significant level of disability within a short period of time (Expanded Disability Status Scale score of 6 within five years). The clinical profile and progression of the disease were analyzed in a Brazilian cohort of 293 patients. Twenty-five (8,53%) patients were found to have MMS and were compared with the remaining 268 (91,47%). Women, non-white patients, older age at disease onset, shorter intervals between the first attacks, and more attacks in the first two years of the disease were all more common in the MMS group. These findings could serve as prognostic factors when making therapeutic decisions.