While platelets are well known to play a central role in hemostasis and thrombosis, there is emerging experimental evidence to suggest that they also mediate tumor cell growth, angiogenesis and metastasis. The receptor for advanced glycation end products (RAGE) has been extensively reported in many tumor types and initiates a downstream proinflammatory signaling cascade. RAGE ligands are expressed and secreted by tumor cells and are associated with poorer outcomes in a wide variety of tumors. In addition RAGE has been identified on human platelets and RAGE ligands may contribute to platelet activation. Therefore in the tumor microenvironment, upon activation, activated platelets interact with tumor cells through paracrine signaling and direct contact, thereby promoting tumor cell growth and thrombosis. Therefore, according to what is mentioned in this article, RAGE expression and its ligands could be a useful serological biomarker for diagnosis and treatment of cancer, as well as molecular target for novel forms of therapies.