In myelofibrosis, both angiogenesis and myeloproliferation constitute the expression of neoplastic growth. A significant proportion of endothelial cells lining the spleen microvasculature harbors the JAK2V617F mutation. The figure illustrates how mutated endothelial cells, producing abnormally high levels of adhesion molecules such as ICAM-1, V-CAM, and E-selectin, might represent the “neoplastic” vascular niches where trapped hematopoietic stem cells are forced to proliferate. Indeed, in spleen microenvironment, neoplastic myeloproliferation and angiogenesis are tightly interrelated.