How to make an accurate diagnose of multiple sclerosis (MS) is a challenging clinical problem. Although many guidelines and consensus have clearly defined the typical imaging characteristics of MS, other neurological diseases are often misdiagnosed as MS due to the interference of untypical manifestations and radiological mimickers in clinical practice. Cerebral small vessel disease (CSVD) is likely to be misdiagnosed as MS due to its similarity in clinical manifestations and radiological pattern. By reviewing the misdiagnosed cases reported in the previous literature, it is found that the atypical imaging manifestations of hereditary CSVD and acquired CSVD can mimic MS and lead to misdiagnosis in satisfying the diagnostic criteria for MS. However, through research in the pathologic mechanism, it reveals that MS and CSVD have corresponding characteristics and there are distinct differences in morphology and distribution of the white matter hyperintensity between MS and CSVD. Such differences in imaging manifestations reflect the discrepancy in the pathogenesis of two kinds of diseases. This paper reviews the cases of CSVD misdiagnosed as MS reported in the previous literature, and discusses the similarities and differences between them from the perspective of imaging features and pathological mechanism, so as to help clinicians better distinguish MS from CSVD and avoid misdiagnosis.