Human osteopontin (OPN) is a glycosylated phosphoprotein which is expressed in a variety of tissues in the body. In recent years, accumulating evidence has indicated that the aberrant expression of OPN is closely associated with tumourigensis, progression and most prominently with metastasis in several tumour types. In this review, we present the current knowledge on the expression profiles of OPN and its main splice variants in human cancers, as well as the potential implications in patient outcome. We also discuss its putative clinical application as a cancer biomarker and as a therapeutic target.