Multiple sclerosis can usually be diagnosed from a patient's history, clinical examination, cerebrospinal fluid (CSF) analysis, and observations from magnetic resonance imaging (MRI). However, sometimes, the classic clinical criteria, even when supported by MRI findings or by abnormalities of the CSF, may not be sufficiently specific. Many conditions can produce a multifocal central nervous system syndrome with a relapsing-remitting course in young adults. The rate of misdiagnosis is around 5%, indicating that 1 in 20 patients thought to have MS have instead a condition resemling MS. The need to reach diagnostic certainty is particularly important given the availability of treatments which may potentially prevent the progression of the disease. Therefore, the search for new methodological approaches which increase the sensitivity and specificity of the diagnosis is warranted. While waiting for the development of new techniques to facilitate an early and correct diagnosis, a correct approach to a suspect MS patient has to be underlined in order to reduce the risk of a misdiagnosis. In this paper, I illustrate the diagnostic work-up that the practicing physician should follow when first confronted by a patient suspected of having MS.