We report four cases of biopsy-proven B-cell-rich primary angiitis of the central nervous system (PACNS). The mean age of the patients was 29 years (range, 23-37 years). The patients suffered from unilateral weakness (n = 2), seizure (n = 1), and hypersomnia, anorexia and confusion (n = 1). The vital signs and the results of laboratory tests were within normal limits in all the four cases except erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). ESR was elevated in one patient and CRP was elevated in two patients. The magnetic resonance imaging (MRI) scans revealed single (n = 2) or multiple (n = 2) irregularly enhancing lesions. Radiological studies initially indicated tumors such as glioma (n = 2) or lymphoma (n = 1), except in one case, in which the radiological analysis indicated vasculitis or demyelinating disease. All the cases involved both medium-sized (50-250 microm in diameter) and small-sized vessels (20-49 microm in diameter). The vascular, perivascular and parenchymal lymphocytes were polymorphous; however, CD20-positive B-cells were predominated in blood vessels while the CD8-positive T-cells infiltrated predominantly in brain parenchyma. Therefore, our patients revealed B-cell dominant lymphocytic vasculitis. Two patients who underwent active treatment (corticosteroid alone or with cyclophosphamide) showed remarkable clinical and radiological improvement but two patients still have initial neurological symptoms, namely, confusion and newly developed seizures, respectively, during the 19-101-month follow-up periods; this effect can be attributed to irreversible brain damage. Therefore, although early brain biopsy may be associated with histopathologic diagnostic pitfalls, it is a mandatory procedure for obtaining a confirmative diagnosis as well initiating early therapy, thereby reducing brain damage.