Ten-Eleven Translocation-2 (TET2) encodes a dioxygenase that converts 5-methyl-cytosine (5-mC) to 5-hydroxymethyl-cytosine (5-hmC) and promotes DNA demethylation. TET2 is a tumor suppressor gene and loss-of-function via mutations, deletion and IDH1/2 (Isocitrate Dehydrogenase 1 and 2) gene mutations is a common event in myeloid and lymphoid malignancies. TET2 is also present in about 10% of otherwise healthy elderly individuals with clonal hematopoiesis of indeterminate potential (CHIP) and in some patients with unexplained cytopenia but who do not satisfy diagnostic criteria for MDS, so-called clonal cytopenia with undetermined significance (CCUS). Mutations in TET2 occur in 50-60% of chronic myelomonocytic leukemias. Comutation of TET2 and SRSF2 was highly predictive of a myeloid neoplasm characterized by myelodysplasia and monocytosis, including but not limited to, chronic myelomonocytic leukemia. TET2 mutations are also found in 20-40% of systemic mastocytosis, 36% of blastic plasamcytoid dendritic cell neoplasm, 12-32% of acute myeloid leukemia, 10-20% of primary myelofibrosis, 10-33% of myelodysplastic syndromes, 10% of myelodysplastic/myeloproliferative neoplasms with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T), 22% of polycythemia vera, and 16% of essential thrombocythemia. TET2 mutations are absent in juvenile myelomonocytic leukemia and show a low prevalence (less than 5%) in pediatric AML. Among lymphoid neoplasms, TET2 mutations are reported in approximately 30% of angioimmunoblastic lymphomas and less than 15 % of other mature T cell lymphomas and mature B cell lymphomas. In general, the mutations in TET2 are typically loss of function variants (frameshift, missense, nonsense mutations) that may be monoallelic or biallelic and occur throughout the gene. TET2 mutations tend to be mutually exclusive of mutations in IDH1/IDH2. TET2 mutations are associated with unfavorable outcomes and shorter survival after hematopoietic stem cell transplantation in patients with myelodysplastic syndrome (PMID: 25092778). In acute myeloid leukemia with wild-type FLT3-ITD and normal karyotype or intermediate-risk cytogenetic abnormalities, TET2 mutations are associated with an unfavorable prognosis.