Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous clinicopathologic entity accounting for 30% of non-Hodgkin's lymphomas. The pathogenesis of DLBCL is complex and heterogeneous. Recent studies using analysis of global gene expression with DNA microarrays and the classical molecular approaches demonstrate presence of several DLBCL subtypes characterized by different cells of origin, cytogenetic and molecular aberrations, and distinct pathogenesis. This review summarizes the progress in understanding of DLBCL biology and presents a state-of-the-art overview of DLBCL molecular pathogenesis.