The discovery of genomic TET2 variants in CLPD-NK has redefined the understanding of the clonal evolution in 2 major subsets of the disease. Fish plots capture the postulated clonal hierarchy of STAT3-mutated (A) and TET2-mutated (B) CLPD-NK. Until recently, the mechanistic model of CLPD-NK had been centered on pronounced cytokine exposure of the precursor cell and/or its gain-of-function STAT3 SH2 domain mutations, both leading to constitutive STAT activation (beige = myeloid/lymphoid precursor cells; green = STAT3-mutated clone). Pastoret et al provide evidence of highly recurrent loss-of-function TET2 mutations in CLPD-NK (34%) and in the myeloid compartment of affected cases. Such TET2 lesions are likely to have their origin in common progenitor cells. Generally, they are frequent nonconsequential constituents of a CHIP and are also likely under the right conditions to give rise to myeloid and NK/T-cell neoplasms (beige = myeloid/lymphoid precursor cells; red = TET2-mutated clone; blue = DNMT3A-mutated clone). TET2-mutated cases are obviously distinct, histogenetically and clinically. In fact, TET2-mutated cases presented with lower platelet counts, a CD16^low phenotype, an “AITL-like” transcriptome, and more frequently other malignant hematologic diseases, whereas the almost mutually exclusive STAT3-mutated cases (27%) were characterized by anemia, lower neutrophil counts, a cytotoxic CD16^highCD57^neg pattern, and a gene expression signature that resembles STAT pathway activation. Professional illustration by Somersault18:24.