Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma. BCL2 apoptosis regulator (BCL2) and marker of proliferation Ki-67 (Ki-67) are established prognostic markers, which have traditionally been assessed separately in DLBCL. However, no studies have evaluated the prognostic value of the combination of BCL2 and Ki-67 index. Thus, the present study aimed to analyze the prognostic value of combination of these two markers. Immunohistochemical analysis was used to assess the expression of BCL2 and Ki-67 in 274 cases of DLBCL. The BCL2/Ki-67 index demonstrated a significant association with decreased overall and progression free survival of patients with DLBCL, particularly for the germinal center B-cell-like subtype of DLBCL. Following multivariate analysis, the BCL2/Ki-67 index retained prognostic significance. Patients with coexpression of BCL2 and Ki-67 constituted a unique group with poor survival, thus novel therapies targeting BCL2 protein and high proliferative activity may improve the outcome of these patients.