The most common myeloproliferative syndrome, this is characterized by an increase in red blood cell (RBC) mass, massive splenomegaly, and clinical manifestations related to increased blood viscosity, including neurologic symptoms (vertigo, tinnitus, headache, visual disturbances) and thromboses (myocardial infarction, stroke, peripheral vascular disease; uncommonly, mesenteric and hepatic). It must be distinguished from other causes of increased RBC mass (Chap. 45. Anemia and Polycythemia). This is most readily done by assaying serum erythropoietin levels. Polycythemia vera is associated with very low erythropoietin levels; in other causes of erythrocytosis, erythropoietin levels are high. Assays for the JAK2(V617F) mutation are now widely available. Pts are effectively managed with phlebotomy. Some pts require splenectomy to control symptoms, and those with severe pruritus may benefit from psoralens and UV light. 20% develop myelofibrosis, <5% acute leukemia. An inhibitor of JAK1 and JAK2, ruxolitinib, is being tested.