Objective To investigate the prognostic significance of CD5 and B cell lymphoma/leukemia protein-2 (Bcl-2) in the elderly patients with diffuse large B cell lymphoma (DLBCL). Methods A retrospective cohort study was carried out on 35 patients(＞60 years old) who were diagnosed as DLBCL at Department of Hematology of Xijing Hospital from January 2007 to December 2013. The patients were followed up for 2 years. The clinicopathological data and prognosis were recorded, and the expression of CD5 and Bcl-2 was detected by immunohistochemistry. Patients were divided into groups according to the positive expression of CD5 and Bcl-2 (positive tumor cell >30%), central nervous system (CNS) involvement or not, clinical stage of the tumor, and survival of each group was compared. SPSS statistics 22.0 was used for data processing, Fisher test for intergroup comparison, Kaplan-Meier method for the survival curve, Log-Rank method for single factor analysis between the curves, and Cox regression model for multivariate analysis.Results Three cases were lost with a loss rate of 8.6%. The positivity rate were 21.9%(7/32) for CD5,6.9%(15/32) for Bcl-2 and 15.6%(5/32) for both. CNS involvement was found in 21.9%(7/32) patients. The tumor was stage Ⅲ in 10 patients and stage Ⅳ in 22 patients. The median overall survival (OS) was 24 months, and median progression free survival (PFS) was 18 months.The 1-year survival rate was 96.9%(31/32) and 71.9%(23/32) for 2 years. Univariate analysis showed that OS and PFS were lower in CD5⁺ and Bcl-2⁺ patients (P<0.05) than CD5- and Bcl-2- patients, but no significant difference was found between the patients at Stage Ⅲ and those at Stage Ⅳ in PFS (P=0.055) and OS (P=0.076). In addition, the rate of CNS involvement was significantly higher among CD5⁺ patients than that of CD5- patients (57.1% vs 12.0%; P=0.026), and significantly higher among Bcl-2⁺ patients than that of Bcl-2- patients (40.0% vs 5.9%; P=0.033). Multivariate Cox analysis showed that CD5⁺ was an independent risk factor for OS in patients with DLBCL (OR=11.205,5%CI 1.717-73.112; P=0.012). Conclusion CD5⁺ can be an independent risk factor for poor prognosis of the elderly DLBCL patients. It is of important clinical value for the prognosis and the choice of future treatment strategies.