Multiple sclerosis (MS) has been increasingly reported in association with other autoimmune diseases not primary affected the nervous system. The coexistence of MS and systemic sclerosis (SSc) has been rarely described. We report here the case of a 46-year-old female patient with longstanding MS since the age of 26, who developed SSc 12 years later. Her MS was of the relapsing-remitting type, but the definite diagnosis was not made until the age of 33. MS diagnosis was based on medical history, magnetic resonance imaging (MRI) studies and positive cerebrospinal fluid analysis. One year after the diagnosis of MS, she developed Raynaud's phenomenon, skin tightness and hypopigmented patches, suggestive of scleroderma. Further investigation with laboratory studies, including serology, hand and chest X-rays, and chest computerized tomography scan confirmed the SSc diagnosis. Our report highlights the interesting association between MS and SSc that may be due to an overlapping pathogenetic mechanism for both processes.