Osteopontin (opn) is a glyco-phosphoprotein that is expressed and secreted by numerous human cancers. Opn has pivotal role in cell adhesion, chemotaxis, prevention of apoptosis, invasion, migration and anchorage-independent growth of tumor cells. Extensive research has demonstrated the pivotal role of opn in regulation of cellular signaling, which controls neoplastic and malignant transformation. The elevated expression of opn has been observed in a variety of cancers. Recently, substantial evidence has linked opn with tumor metastasis and poor prognosis. However, the understanding of the molecular mechanisms that define the role of opn in cell invasion and metastasis is incomplete. The following review will discuss the molecular structure of opn, its function role in tumor cell metastasis and its downstream target genes that activate invasive mechanisms. Understanding of the role of opn in neoplastic transformation and its cellular target genes may enable development of novel anti-cancer therapy approaches.