Demyelinating diseases of the central nervous system include a wide spectrum of different disorders that may resemble multiple sclerosis (MS). The diagnosis of MS is based on typical clinical and paraclinical criteria. The simplified McDonald's criteria, which combine clinical picture, NMR findings, CSF analysis and visual evoked potentials, are appropriate for daily neurologic routine. If some of these criteria are atypical, diagnostic algorithm should be extended to some other procedures to exclude other diseases that can mimic MS not only in symptoms, signs or course of the disease but also in laboratory findings. In such a case, an alternative, better explanation for the clinical manifestations should be considered and performing specific tests is helpful to exclude alternative diagnoses.