We recently found that a gain-of-function mutation of HIF-2A (c.1589C>T) leads to PPGLs with polycythemia simultaneously (26) and a mutation in HIF-2A immediately distal to its DNA binding domain (p.Ser71Tyr) has been identified in sporadic PPGLs (71) (Figure 1). This evidence concerns the gene EPAS1 and polycythemia.