Sato and colleagues recently identified that the ephrin type B receptor 2 (EPHB2) is present on small EVs secreted by head and neck cancer cells, and that EV-associated EPHB2 stimulates tumor angiogenesis by activating the STAT3 signaling pathway via engagement of ephrin-B2 on the surface of endothelial cells [68]. This evidence concerns the gene EPHB2 and head and neck cancer.