Somatic TET2 mutations (TET2^MT) are frequent in myeloid neoplasia (MN), particularly chronic myelomonocytic leukemia (CMML). TET2^MT includes mostly loss-of-function/hypomorphic hits. Impaired TET2 activity skews differentiation of hematopoietic stem cells toward proliferating myeloid precursors. This study was prompted by the observation of frequent biallelic TET2 gene inactivations (biTET2ⁱ) in CMML. We speculated that biTET2ⁱ might be associated with distinct clinicohematological features. We analyzed TET2^MT in 1045 patients with MN. Of 82 biTET2ⁱ cases, 66 were biTET2^MT, 13 were hemizygous TET2^MT, and 3 were homozygous TET2^MT (uniparental disomy); the remaining patients (denoted biTET2⁻ hereafter) were either monoallelic TET2^MT (n = 96) or wild-type TET2 (n = 823). Truncation mutations were found in 83% of biTET2ⁱ vs 65% of biTET2⁻ cases (P = .02). TET2 hits were founder lesions in 72% of biTET2ⁱ vs 38% of biTET2⁻ cases (P < .0001). In biTET2ⁱ, significantly concurrent hits included SRSF2^MT (33%; P < .0001) and KRAS/NRAS^MT (16%; P = .03) as compared with biTET2⁻. When the first TET2 hit was ancestral in biTET2ⁱ, the most common subsequent hits affected a second TET2^MT, followed by SRSF2^MT, ASXL1^MT, RAS^MT, and DNMT3A^MT. BiTET2ⁱ patients without any monocytosis showed an absence of SRSF2^MT. BiTET2ⁱ patients were older and had monocytosis, CMML, normal karyotypes, and lower-risk disease compared with biTET2⁻ patients. Hence, while a second TET2 hit occurred frequently, biTET2ⁱ did not portend faster progression but rather determined monocytic differentiation, consistent with its prevalence in CMML. Additionally, biTET2ⁱ showed lower odds of cytopenias and marrow blasts (≥5%) and higher odds of myeloid dysplasia and marrow hypercellularity. Thus, biTET2ⁱ might represent an auxiliary assessment tool in MN.