Abstract: To assess the proliferative activity of diffuse large B cell lymphoma ( DLBCL ) using immunohistochemistry ( IHC ) and real-time polymerase chain reaction of Cdc7 and Mcm2 and to explore their potential value in predicting prognosis. Methods: From Jan 2008 to Jan 2010, the clinical characteristics of 60 DLBCL patients were collected using IHC to assess the expression of Cdc7 and Mcm2. A statistical analysis was conducted on the association of Cdc7 and Mcm2 with the clinicopathologic characteristics of DLBCLs. Results: In the univariate analysis, the 2-year overall survival rate of the patients with positive Cdc7 expression was 41%, and the patient with negative Cdc7 expression was 73%, ( P < 0.05 ). The 2-year overall survival rate of the patients with positive Mcm2 expression was 25%, and the patients with negative Mcm2 expression was 75% ( P < 0.05 ). The clinical data were as follows: ECOG performance status ( 0-1 vs. 2 ) ( 76.6% vs. 23.4% ); Ann Arbor stage ( I-II vs. III-IV ) ( 65.0% vs. 35.0%); IPI ( 0-1 vs. ≥2 ) ( 78.3% vs. 21.7%); LDH level ( normal vs. abnormal ) ( 70.0% vs. 30.3%); radiotherapy only vs. chemotherapy combined with radiotherapy ( 41.7% vs. 58.3% ); and GCB subtype vs. non-GCB subtype ( 53.3% vs. 46.7% ). ECOG performance status, Ann Arbor stage, International prognostic index ( IPI ), LDH level, therapy model, and histological type were found to be the prognostic factors associated with the overall surviva1 in DLBCL. The difference in 2-year overall survival rates between the different clinical indicators were significant. The patients with Cdc7- and Mcm2-positive DLBCL had a higher stage of disease than patients with Cdc7- and Mcm2-negative DLBCL. The patients with Cdc7- and Mcm2-positive DLBCL had higher IPI of disease than patients with Cdc7- and Mcm2-negative DLBCL. Conclusion: IPI, treatment, and different cell derivation were prognostic factors. Furthermore, poor disease specific survival is observed in DLBCL patients with high-level Cdc7 and Mcm2 expression.