Thrombocytosis is defined by guidelines as a platelet count of 450 × 10³/μL or greater. It most often results from secondary causes and should resolve with treatment of the underlying condition. Primary thrombocytosis in adults is most commonly due to myeloproliferative neoplasms, including essential thrombocythemia. Thrombocytosis may be identified incidentally in asymptomatic patients or when performing blood tests to investigate symptoms or signs that could indicate microvascular conditions (eg, headaches, paresthesia, erythromelalgia), splenomegaly, thrombosis, and hemorrhage, which are presenting features of essential thrombocythemia. A repeat complete blood cell count with differential and peripheral blood smear should be performed to confirm persistent thrombocytosis and assess other blood cell lines for findings suggestive of myeloproliferative neoplasms. Additional testing, including C-reactive protein levels and iron studies with ferritin levels, should be performed based on history and examination findings. If essential thrombocythemia is suspected in patients with persistent thrombocytosis without an identified cause, testing for Janus kinase 2 gene sequence variations should be performed and, if negative, testing for calreticulin and myeloproliferative leukemia gene sequence variations; a bone marrow biopsy should also be performed. The revised International Prognostic Score of Thrombosis for Essential Thrombocythemia should be calculated to stratify thrombosis risk and guide management, including when to use low-dose aspirin and cytoreductive therapy. Cardiovascular risk factors should also be addressed. Hydroxyurea is the first-line agent in cytoreductive therapy. No treatments have been shown to increase survival or prevent progression to myelofibrosis or leukemia in patients with essential thrombocythemia.