Staphylococcus aureus is the leading etiologic agent of implant orthopedic infections. Until recently S. aureus was considered a mere extracellular pathogen; it then turned out to be able to invade eukaryotic cells. Adhesion of S. aureus to peri-prosthesis tissues represents the starting of the infection pathogenesis and the first step of the subsequent internalization of S. aureus by host cells. In the present work the experimental observations on two epidemic clinical strains differing in their adhesin pattern demonstrate the crucial role of the fibronectin-binding protein A in the internalization process and suggest that CNA and Bbp adhesins can play a synergistic role by acting in the initial adhesion of S. aureus to osteoblasts, thus favoring the subsequent FnBPA-mediated internalization.