Activating EZH2 mutations, which increase total H3K27me3 levels (Sneeringer et al., 2010; Yap et al., 2011), increase tumor survival and growth in pre-clinical models (Béguelin et al., 2013) and are found in up to 24% of diffuse large B cell lymphomas (Morin et al., 2010). The gene discussed is EZH2; the disease is diffuse large B-cell lymphoma.