Recurrent mutations in RNA splicing factors, including SF3B1, SRSF2, and U2AF1, account for 60%–70% of somatic mutations in MDS (1) and are common in myeloproliferative neoplasms (MPNs), the MDS/MPN overlap disorder chronic myelomonocytic leukemia (CMML), and AML (1–6). The gene discussed is U2AF1; the disease is myelodysplastic syndrome.