A simplified flowchart for a diagnostic approach to PV that I use for the investigation of erythrocytosis. Diagnostic procedures indicated with a dotted border require a high level of suspicion and, preferably, reasonable evidence of familial history. These genetics tests are complex, costly, and should be performed in a specialized laboratory. BPG, erythrocyte 2,3-biphosphoglycerate; EPO-R, erythropoietin receptor; HIF-2a, hypoxia-inducible factor 2a; N/I, normal/increased; PDH2, prolyl hydroxylase domain protein 2; SN, subnormal; VHL, von Hippel-Lindau.