This study provides a comprehensive analysis of the coding genome of diffuse large B-cell lymphoma (DLBCL) using next-generation sequencing and copy number analysis. The authors identified an average of over 30 clonally represented gene alterations per case, revealing a high degree of complexity in the DLBCL genome. They found mutations in genes not previously implicated in DLBCL pathogenesis, particularly those involved in chromatin regulation. The study also identified recurrent alterations in genes controlling immune recognition by T cells, such as *B2M* and *CD58*, suggesting a role in tumor escape from immune surveillance. Additionally, the authors observed frequent disruptions in pathways of post-GC differentiation, including the NF-κB and BCL6/BLIMP1 axis, which are crucial for the development of the DLBCL phenotype. These findings highlight the importance of chromatin modifying enzymes and immune recognition genes in DLBCL pathogenesis and suggest potential therapeutic targets.This study provides a comprehensive analysis of the coding genome of diffuse large B-cell lymphoma (DLBCL) using next-generation sequencing and copy number analysis. The authors identified an average of over 30 clonally represented gene alterations per case, revealing a high degree of complexity in the DLBCL genome. They found mutations in genes not previously implicated in DLBCL pathogenesis, particularly those involved in chromatin regulation. The study also identified recurrent alterations in genes controlling immune recognition by T cells, such as *B2M* and *CD58*, suggesting a role in tumor escape from immune surveillance. Additionally, the authors observed frequent disruptions in pathways of post-GC differentiation, including the NF-κB and BCL6/BLIMP1 axis, which are crucial for the development of the DLBCL phenotype. These findings highlight the importance of chromatin modifying enzymes and immune recognition genes in DLBCL pathogenesis and suggest potential therapeutic targets.