This study investigates the role of *CREBBP* and *EP300* genes in the pathogenesis of B-cell non-Hodgkin's lymphoma, specifically follicular lymphoma and diffuse large B-cell lymphoma. The authors found that these genes, which encode histone and non-histone acetyltransferases (HATs), are frequently inactivated by structural alterations such as deletions and mutations in these two types of lymphoma. These lesions are often monoallelic, suggesting that reduced HAT dosage is important for lymphomagenesis. The study demonstrates that these mutations lead to defects in acetylation-mediated inactivation of the BCL6 oncoprotein and activation of the p53 tumor suppressor. These findings highlight *CREBBP/EP300* mutations as a major pathogenetic mechanism in common forms of B-cell non-Hodgkin's lymphoma, with implications for the development of drugs targeting acetylation/deacetylation mechanisms.This study investigates the role of *CREBBP* and *EP300* genes in the pathogenesis of B-cell non-Hodgkin's lymphoma, specifically follicular lymphoma and diffuse large B-cell lymphoma. The authors found that these genes, which encode histone and non-histone acetyltransferases (HATs), are frequently inactivated by structural alterations such as deletions and mutations in these two types of lymphoma. These lesions are often monoallelic, suggesting that reduced HAT dosage is important for lymphomagenesis. The study demonstrates that these mutations lead to defects in acetylation-mediated inactivation of the BCL6 oncoprotein and activation of the p53 tumor suppressor. These findings highlight *CREBBP/EP300* mutations as a major pathogenetic mechanism in common forms of B-cell non-Hodgkin's lymphoma, with implications for the development of drugs targeting acetylation/deacetylation mechanisms.