I have a long trajectory in research of lymphoid neoplasms from a multidisciplinary perspective. We have characterized several new lymphoma entities and disease subtypes widely accepted and included in the current WHO classification. I have been Co-Director of the ICGC- chronic lymphocytic leukemia (CLL) Genome Project (2009-2018) and have participated in the Blueprint Epigenetic European Consortium (2011-16). These projects have made seminal contributions understanding the (epi)genomic alterations of CLL, mantle cell lymphoma (MCL) and other lymphomas. Our major contributions have been the elucidation of the whole genome/ exome sequences, transcriptome, and epigenomic profiling of these neoplasms and define their potential clinical impact in large cohort of patients. These studies have revealed a genomic complexity of unexpected dimensions with the identification of new mutated genes and metabolic pathways involved in cancer, the biological and clinical relevance of mutations in non-coding regions of the genome, and the recognition of new mutagenic mechanisms that are providing clues to interpret the heterogeneous behavior of these diseases. The functional and clinical impact of various genes which had never been considered involved in cancer have been characterized. New disease subtypes, novel biomarkers and expression signatures of clinical relevance and new therapeutic targets have been also identified and are being characterized. Our group has also defined the first multilayer reference epigenomes of different stages of the normal B-cell differentiation process that have been an instrumental framework to understand the epigenome alterations in CLL, MCL and other lymphoid neoplasms. In the last year we have expanded the genomic/epigenomic studies to regions of the genome nor previously analyzed due to the lack of proper bioinformatics tools. In this sense we have developed new pipelines to analyze the complex region of the immunoglobulin gene in lymphoid neoplasms and identified a novel mechanism generating tumor cell diversity based on recurrent mutation of the non-coding U1 spliceosomal RNA in CLL indicating that driver discovery should be extended to a wider range of genomic regions. All these studies are revealing the relevance of drivers in non-coding regions and the crosstalk between genomic and epigenomic alterations in the malignant transformation of lymphoid cells. Our studies have shown that this new approach to global knowledge of the cancer genome opens the prospect of unexpected dimensions in understanding these diseases and establish solid basis for a personalized medicine under a genomic perspective.