The Wnt/β-catenin signaling pathway plays diverse roles in embryonic development and maintenance of organs and tissues in adults as well as in the pathogenesis of a range of diseases, including many types of carcinomas. β-catenin, the principal downstream effector of the Wnt/β-catenin pathway, migrates to the nucleus and mediates the activation of the Wnt/β-catenin pathway. The aim of the present study was to investigate the expression and localization of β-catenin in diffuse large B-cell lymphoma (DLBCL) tissues and to illuminate the role of β-catenin in the pathogenesis of DLBCL. The mRNA expression levels of β-catenin were determined by quantitative polymerase chain reaction (PCR), while β-catenin protein levels were detected by western blot analysis and immunohistochemical staining. DLBCL showed a higher expression of β-catenin in contrast to reactive hyperplasia of lymph node tissues at both the mRNA and protein levels (P< 0.001). Immunohistochemical analysis indicated nuclear localization of β-catenin in 14 (46.67%) DLBCL cases, whereas no inflammatory lymph node tissue showed nuclear accentuation of β-catenin. The overexpression and nuclear accentuation of β-catenin were strongly correlated to the clinical staging of patients with DLBCL (P< 0.05). These results suggest that the Wnt/β-catenin pathway is partly activated in DLBCL and may contribute to its pathogenesis.