Though 70% of CMML patients present without any cytogenetic abnormalities [11, 12] they harbor somatic mutations in genes that influence epigenetic regulation (TET2, DNMT3A, ASXL1, EZH2, IDH1, IDH2), mRNA splicing (SRSF2, U2AF1), genome stability (SETBP1, TP53), transcription regulation (RUNX1, CEBPA, NPM1) and cell signaling pathways (KRAS, NRAS, CBL, PTPN11, JAK2, MPL) [13–17]. The gene discussed is CBL; the disease is chronic myelomonocytic leukemia.