Introduction: Diffuse large B-cell lymphoma (DLBCL), not otherwise specified, is a large B-cell lymphoma with a diffuse growth pattern and aggressive clinical course. It is divided in subgroups according to its morphology, immunophenotype, and primary site. Dissemination to bone marrow occurs in 11% to 35% of cases and can be of concordant or discordant morphology. Objective: To examine the association, the type of bone marrow involvement in relation to the primary site, morphology, immunohistochemistry of DLBCLs and to determine the cases of Epstein-Barr virus positive DLBCLs. Materials and Methods: We reviewed lymph node and extranodal biopsies as well as the respective bone marrow biopsies in all cases of DLBCL diagnosed in the Hospital General de México during the period from 2002 to 2010. We used immunohystochemistry for immunophenotype identification (Hans's algorithm) and an in-situ hybridization technique to detect presence of Epstein Barr encoded RNA (EBER). Results: We included 108 patients with a mean age of 51.9 years, 59 (55%) were men. DLBCL involved lymph nodes in 60% of cases and palatine tonsils in 13%. The centroblastic variant predominated (80%) and 58% originated from activated B-cells. Infiltration of bone marrow was present in 30% of cases and was discordant in 55% of these cases. Correlation between morphology and bone marrow infiltration was statistically significant (P = 0.0003). Presence of Epstein-Barr virus was demonstrated in 15% of patients older than 50 years. Conclusions: Dissemination to bone marrow occurred in 30% of cases and discordant involvement was most common. DLBCL originating from activated B-lymphocytes predominated and the most common extranodal sites were palatine tonsils, suggesting that our population has a clinical behavior similar to Asiatic populations.