According to the World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues, diffuse large B-cell lymphoma comprises about 40% of adult cases of non-Hodgkin s lymphoma. It consists of the following morphological variants: 1) centroblastic (with or without multilobulated nuclei); 2) immunoblastic (>90% of immunoblasts); 3) T cell/histiocytes rich; and 4) anaplastic. Rare morphological variants plasmablastic type, mediastinal (thymic) diffuse large B-cell lymphoma, intravascular, and primary effusion B-cell lymphoma are considered distinct variants of diffuse large B-cell lymphoma due to their unique topographic presentation and clinical behavior, as well as immunophenotypic and genetic characteristics. T-cell/histiocyte-rich B-cell lymphoma is morphologically characterized by up to 25% of large neoplastic B cells and 75-90% of reactive, non-neoplastic T cells. Mediastinal (thymic) diffuse large B-cell lymphoma is considered a subtype of diffuse large B-cell lymphoma arising in the mediastinum, with distinctive morphological, immunohistochemical, genotypic, and clinical features. Mediastinal diffuse large B-cell lymphoma is an aggressive disease with poor outcome, which probably originates from thymic B cells at the terminal stage of differentiation. During the 1997-2001 period, 720 patients were diagnosed with non-Hodgkin s lymphoma in our institution. Out of 101 (14%) patients with diffuse large B-cell lymphoma, 17 had T-cell-rich B-cell lymphoma and their median survival was less than 20 months, with no difference regarding sex, bone marrow involvement, CD30 positivity, or histiocytic component of the tumor. Twenty out of 101 patients had mediastinal B-cell lymphoma and their median survival was 21 months, with sex or degree of necrosis of the involved lymph node having no impact on survival. We studied the frequency of bcl-2 gene rearrangement in fusion with immunoglobulin receptor gene of t(14;18) and found no such event among 20 of our patients with mediastinal diffuse large B-cell lymphoma. Despite extensive efforts and constant progress in our understanding of non-Hodgkin s lymphoma pathogenesis, the diffuse large B-cell lymphoma group remains heterogeneous entity awaiting further pathological and clinical stratification.