The search for highly sensitive and highly specific biomarkers of MS, including neuroimaging biomarkers, continues. One of such biomarkers is the central vein sign detectable on SW and T2-weighted MR images. The sensitivity and specificity of methods used for central vein sign detection vary. This article describes two clinical cases of patients with similar neurological symptoms which required making differential diagnosis between multiple sclerosis and secondary demyelination in the presence of a systemic disorder (systemic lupus erythematosus). In addition to routine MR sequences, we used SWI generated by a 3T scanner. The lesions with the central vein sign were counted; the proportion of perivenular lesions was determined. In the multiple sclerosis case, all the lesions were perivenular; the proportion of lesions with the central vein sign in the patient with secondary demyelination in the presence of systemic lupus erythematosus was 16.7%. The use of SW images improved the informative value of the analysis.