Sirtuin1 (SIRT1) is a nicotinamide adenine dinucleotide-dependent deacetylase. Recently, it is suggested that SIRT1 may be involved in the development of malignant tumors including mouse lymphoma. Therefore, we investigated the prevalence and the prognostic impact of SIRT1 expression in diffuse large B-cell lymphoma (DLBCL). Immunohistochemical expression of SIRT1, p53, bcl2, CD10, bcl6, and multiple myeloma-1 (MUM1) were evaluated by using a 2 mm core from 104 DLBCL patients for tissue microarray. Positive expression of SIRT1 was seen in 74% (77/104) of patients. In total DLBCL patients, SIRT1 and p53 expression were significantly associated with shorter overall survival (OS) by univariate analysis (P=0.001 and P=0.011, respectively). SIRT1 was also an independent prognostic factor by multivariate analysis (P=0.01). According to the expression patterns of CD10, bcl6, and MUM1, germinal center B cell (GCB) types were represented in 38 cases (37%) and non-GCB types were represented in 66 cases (63%). In the GCB type, only p53 expression was associated with a significantly shorter OS (P=0.032). In the non-GCB type, expression of SIRT1 correlated with shorter OS by univariate analyses (P=0.005) and multivariate analyses (P=0.049). In conclusion, we showed that SIRT1 expression is a clinically significant prognostic indicator for DLBCL patients.