In diffuse large B-cell lymphoma (DLBCL), the germinal center B-cell (GCB) subtype is associated with a better prognosis compared with the nongerminal center B-cell-like (non-GCB) subtype. However, validity of this immunohistochemical subgrouping in primary DLBCL of the central nervous system is unclear. A total 45 cases of primary central nervous system lymphoma (PCNS)/DLBCL were selected, and immunohistochemistries for CD10, Bcl-6, MUM1, and Ki-67 were performed. Each of the cases was subclassified as either GCB or non-GCB based on its immunoprofile. Among clinical and immunologic markers, patients under 70 years of age and who had methotrexate chemotherapy showed a significantly better overall survival (OS). High Ki-67 (ie, a Ki-67 index ≥90%) was an independent prognostic factor for a poor OS in the whole cohort and in the patients with non-GCB subtype tumors (P=0.017, HR=4.267, 95% CI, 1.3-14.0; P=0.031, HR=3.752, 95% CI, 1.3-12.5). Tumors were dominantly non-GCB subtype (41/45, 91.1%); only 4 (8.9%) were GCB subtype. The 2-year OS rates for these groups were 73% and 100%. There was, however, no statistically significant difference between these groups for OS and progression-free survival. The subclassification of PCNS/DLBCL into GCB and non-GCB subtypes did not seem to have a prognostic value. In non-GCB subtype PCNSL patients, high Ki-67 index was an adverse independent prognostic marker that could be used to stratify patients for more suitable management.