The scenario regarding potentially malignant disorders has recently been complicated by the increasing incidence of squamous cell carcinoma of the oral cavity in the younger population without any clear etiology. The changes may be at the molecular, genetic or immunologic levels. Nowadays, the importance of tumor markers is being increasingly felt for diagnostic and prognostic purposes in such conditions. SIBLING proteins play an important role in immune mechanisms and help in regulatory pathways of the body. Osteopontin induces endothelial cell migration and acts in subset of migratory pathways.It also play a important role in the process of angiogenesis. In this book, immunohistochemical role of OPN as a SIBLING protein has been studied, & its role in diagnosis and prognosis of Oral premalignancies and malignancies has been discussed.