Objective　To dissect the clinical and imaging differences between atypical multiple sclerosis and cerebral small vessels diseases.Methods　We presented one case of a hereditary cerebral small vessel disease-autosomal dominant genetic disease combined with subcortical infarction and white matter encephalopathy (CADASIL),which was initially misdiagnosed as multiple sclerosis.Afterwards.We reviewed literature regarding typical images and clinical aspects in multiple sclerosis and cerebral small vessels diseases and discussed the differential diagnosis points.Results　Multiple sclerosis often starts in young adults,with IgG index greater than 0.7,positive oligoclonal band,central venous signs,few microbleeding and asymmetric periventricular white matter lesions on MRI scan.On the contrary,cerebral small vessel diseases often start in old patients with vascular risk factors.MRI scan often shows the lacunar cerebral infarction,microbleeding,brain atrophy and symmetric periventricular white matter hyperintensity.Conclusion　Understanding the differential points between the two diseases may help avoid misdiagnosis and initiate reasonable treatment immediately.