Objective: The primary objective of this study was to analyze the anatomic distribution, clinical features and outcome of Diffuse large B-cell lymphoma (DLBCL) Patients according to the primary site (extranodal vs. nodal) with applicability of International Prognostic Index (IPI). Methodology: A retrospective review (1988 to 2004) of 557 cases of DLBC. Results: The median age was 48.7 +/- 15.3 years, M:F ratio was 2:1. The distribution according to the primary site was: lymph node (N-NHL), 322 cases (58%) of which 145(44%) were stage IV, 76(23%) stage III, 60 (18%) stage II and 47 (15%) stage I. The extra nodal sites (EN-NHL) 235 (42%) cases included gastro-intestinal tract (44%), upper aerodigestive tract (19%), bones (8%), spine (5%), and unusual sites less than 3% each as breast, CNS, testis, lungs and skin. The median survival rate was 4.8 years and 6.3 years in N-NHL and EN-NHL respectively. In the latter this varied greatly depending on the primary site and stage of disease at presentation. In the univariate analysis factors associated with good prognosis were: age less than 60 years, early stage (I-II), extranodal involvement primarily gastric or bone, 0-1 extranodal site, 0-1 performance status, lack of B symptoms and normal LDH level. In the multivariate analysis age, performance status, stage of disease and level of LDH were the main variables predicting overall survival, no nodal or extranodal site maintained their prognostic value. Conclusion: Patients with EN-NHL present more frequently with early stage disease then those with N-NHL, overall survival in both groups largely depended on IPI and not on the site of origin of the malignancy.