In past years, substantial insight regarding the pathogenesis of diffuse large B-cell lymphoma has been obtained. Particularly, based on gene expression profile analysis, this disease can be classified into distinct phenotypic subgroups and specific transcriptional programs have been identified. New technologies like next-generation whole genome/exome sequencing and genome-wide single nucleotide polymorphism array analysis have revealed novel lesions involved in the pathogenesis of this disease. This review focuses on the diversity of genetic lesions identified in the different subtypes of diffuse large B-cell lymphoma.