INTRODUCTION: Classic BCR/ABL1-negative myeloproliferative neoplasms (MPNs) are characterized by clinical and genetic heterogeneity and include 4 distinct constituents. Very little data on clinical presentation and epidemiology of the same is available from the Indian setting. PATIENTS AND METHODS: Patients referred to Hematology-Oncology from January 2018 to August 2020 with suspected MPNs were included in the analysis and prospectively followed-up. All patients were initially screened, and only those meeting the updated World Health Organization 2016 criteria were included in the analysis. Epidemiologic, clinical, and molecular characteristics were documented, and patients were followed-up prospectively. RESULTS: A total of 233 patients were referred for evaluation of MPN, of which 63 were included in the analysis, including 39 males and 24 females. The median age at diagnosis was 57 years (range, 28-82 years), and 38% patients were younger than 50 years of age. The most common presentations were incidental detection in 35 (55.5%), abdominal symptoms in 13 (20%), fatiguability in 7 (11%), and recent vascular events in 6 (9.5%) patients. Final diagnosis was polycythemia vera in 27, essential thrombocytosis (ET) in 21, prefibrotic myelofibrosis in 9, and myelofibrosis in 6 patients. The frequency of driver mutations in polycythemia vera included JAK2 in 75%; in ET, JAK2 in 33%, CALR in 33%, and MPL in 4%; and in prefibrotic myelofibrosis, JAK2 in 66% and CALR in 33%. Aspirin was used for all patients along with risk-adapted cytoreduction with hydroxyurea. Ruxolitinib was reserved for symptoms refractory to hydroxyurea. After a median follow-up of 15 months (interquartile range, 10-28 months) from diagnosis, disease progression was noted in 4 patients. Two patients died at the end of the follow-up period, including 1 with secondary acute myeloid leukemia post myelofibrosis and one with ET and coexistent oral malignancy. The remaining 61 patients are alive and on regular treatment. RESULTS: This is one of the first systematic descriptions and prospective follow-up of patients with BCR/ABL-negative MPNs from India. Our study indicates a younger median age of presentation and higher proportion of JAK2-unmutated disease across all subtypes. The primary role of bone marrow morphology and supportive role of somatic mutations in differentiating MPN subtypes is indicated. CONCLUSIONS: This study sets the stage for a collaborative registry for defining epidemiologic data and long-term outcomes with MPN in India.