Background: Diffuse large B-cell lymphoma (DLBCL) is considered the most common lymphoid malignancy that represented about 35 % of adult nonHodgkin lymphomas (NHL). Although most patients can be cured with the Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisolone (R-CHOP) regimen, many patients die due to relapsed disease. In this study, we aim to assess the clinicopathological characteristics of relapsed DLBCL, not otherwise specified (NOS). Methods: This is a retrospective study conducted on 16 cases of relapsed DLBCL (relapsed group). Meanwhile, 27 cases with DLBCL who capable of attaining complete remission (CR) for 36 months were used as control (CR group). Results: clinically, most patients in the relapsed group were male (62.5%). The relapsed group had a significant difference in comparison to the CR group as regard bone marrow involvement (P = 0.003), serum lactate dehydrogenase (LDH) level (P = 0.005), B symptoms (P = 0.007), performance status (PS) (P = 0.008), international prognostic index (IPI) (P = 0.000) and age-adjusted IPI (P = 0.017). Pathologically, relapsed DLBCL was associated with negative CD10 expression (P = 0.001), negative BCL6 expression (P = 0.047), and nongerminal center B-cell (non-GCB) phenotype (P = 0.018). Conclusions: patients with bone marrow involvement, abnormal serum LDH level, B symptoms, poor PS, intermediate to high IPI & AA-IPI, non-GCB phenotype, lower CD10, and BCL6 expression are more likely to relapse.