We report the case of a woman who started complaining of depression, attention and memory problems at the age of 49. Over the following 6 years, serial neuropsychological assessments showed fluctuating, but overall progressively worsening, performances in tests exploring attention, working memory, language and executive functions. Cerebrospinal fluid (CSF) examination showed identical IgG oligoclonal bands in serum and CSF. Neurological examination, to date, only reveals minimal pyramidal and cerebellar signs. Although typical clinical and laboratory evidence indicating a diagnosis of multiple sclerosis (MS) in this patient is lacking, an extensive diagnostic work-up ruled out many other causes of leukoencephalopathy and neuroradiological features strongly suggest this diagnosis. Multiple sclerosis may present with cognitive or neuropsychiatric symptoms; this should be kept in mind, especially in younger patients, even in the absence of "classical" physical symptoms.