The serum levels of several angiogenic cytokines are increased in patients with Waldenström macroglobulinemia (WM). Angiopoietin-2 is also increased and the balance of angiopoietin-1/angiopoietin-2, which antagonize for the receptor tyrosine kinase Tie-2 is in favor of angiopoietin-2. Lymphoplasmacytic cells may produce VEGF, but they also produce large amounts of CCL-3 which attracts macrophages, and probably mast cells. Mast cells support lymphoplasmacytic cells and may also produce VEGF. VWF is stored in the Weibel-Palade bodies together with several other mediators, including angiopoietin-2. The endothelial cells (ECs) release the content of Weibel-Palade bodies in response to stimuli, such as VEGF and VWF and other molecules (such as angiopoitein-2) are released simultaneously. VWF may also have an inhibitory activity in the constitutive VEGFR-2–dependent pathway(s), which promote EC migration.