The interactions between extracellular matrix fibronectin and various integrins through specific receptors are of fundamental importance in cellular response, cell-cell interactions, immunological and inflammatory events and thrombus formation. The integrin binding domains of FN have been widely investigates and they are represented by the Arg-Gly-Asp (RGD) domain and the nearby areas that help to extend the contact surface, represented by the Pro-His-Ser-Arg-Asn (PHSRN) domain, found in the 9th and 10th type III FN modules. The ability to modulate the various aspects of cellular adhesion, motility and proliferation identified the FN-IN interactions as potential target for therapeutic treatments, especially in cancer and associated conditions (like thrombosis, angiogenesis, osteoporosis).