Among patients with a diagnosis of MDS/MPN overlap syndrome, 84% of which had CMML, presence of mutations in EZH2 (HR 28.5, 95% CI 1.78–455.65, p = 0.018) and TP53 (HR 6.6, 95% CI 1.26–34.43, p = 0.025) as well as increased number of mutations, particularly if more than 3 (HR 3.5, 95% CI 1.09–11.19, p = 0.035) where associated with shorter overall survival. The gene discussed is EZH2; the disease is chronic myelomonocytic leukemia.