Based on the symptoms, especially those affecting small vessels, it is difficult to distinguish multiple sclerosis (MS) from primary angiitis of the central nervous system (PACNS). Magnetic resonance imaging (MRI) helps understand the characteristics of deep gray matter lesions (DGML) in MS and PACNS. We aimed to compare the MRI characteristics of thalamus and basal ganglia lesions between relapsing-remitting MS and PACNS. In our study, 49 relapsing-remitting MS patients and 16 PACNS with MRI-confirmed thalamus or basal ganglia lesions were enrolled. Among the DGMLs in basal ganglia, putamen had significantly higher (P = 0.037) involvement in PACNS than in MS. More importantly, larger lesion sizes in thalamus helps to distinguish PACNS (12.4 ± 4.3 mm) from MS (7.9 ± 3.7 mm) (P = 0.006). But using lesions in basal ganglia, researchers were unable to differentiate the two disorders. Presently, our study shows that MRI performances of deep gray matter differ between MS and PACNS.