High-throughput DNA sequence analysis was used to screen for TET2 mutations in bone marrow-derived DNA from 239 patients with BCR-ABL-negative myeloproliferative neoplasms (MPNs). Thirty-two mutations (19 frameshift, 10 nonsense, 3 missense; mostly involving exons 4 and 12) were identified for an overall mutational frequency of∼ 13%. Specific diagnoses included polycythemia vera (PV; n= 89), essential thrombocythemia (ET; n= 57), primary myelofibrosis (PMF; n= 60), post-PV MF (n= 14), post-ET MF (n= 7) and blast phase PV/ET/MF (n= 12); the corresponding mutational frequencies were∼ 16, 5, 17, 14, 14 and 17%(P= 0.50). Mutant TET2 was detected in∼ 17 and∼ 7% of JAK2V617F-positive and-negative cases, respectively (P= 0.04). However, this apparent clustering of the two mutations was accounted for by an independent association between mutant TET2 and advanced age; mutational frequency was∼ 23% in patients⩾ 60 years old versus∼ 4% in younger patients (P< 0.0001). The presence of mutant TET2 did not affect survival, leukemic transformation or thrombosis in either PV or PMF; a correlation with hemoglobin< 10 g per 100 ml in PMF was noted (P= 0.05). We conclude that TET2 mutations occur in both JAK2V617F-positive and-negative MPN, are more prevalent in older patients, display similar frequencies across MPN subcategories and disease stages, and hold limited prognostic relevance.