Osteopontin, a glycoprotein, was first identified in 1986 in osteoblasts. It is a multifunctional protein, highly expressed in bone. It has many functions on bone mineralization, regulation of immune cell function, inhibition of calcification, control of tumor cell phenotype and cell activation. Osteopontin has been involved in the pathogenesis of many skin diseases as systemic lupus erythematosus, infection, psoriasis, contact dermatitis and cancer. Some of these diseases are discussed in this review.