The involvement of the urokinase-type plasminogen activator (uPA) system in particular has been extensively studied in the pathogenesis of cancer. The molecular role of the uPA receptor (uPAR) is well characterized with its participation in cell migration and extracellular matrix (ECM) degradation. Over-expression of uPAR in cancer has been demonstrated in many studies and is considered an attractive target for anticancer agents. We and others have down-regulated uPAR expression in an attempt to inhibit cancer metastasis based on its molecular role. Uniquely, uPAR which is a glycosyl phosphatidylinositol anchored protein is not only bound to the cell surface but also has a soluble form, suPAR. There is now accumulated clinical and experimental evidence supporting the significant role of uPAR and its soluble counterpart in a number of solid cancers. The expression of uPAR can be associated with tumor cells or stromal cells or both. Differences observed in the expression of uPAR using immunohistochemistry (IHC) are likely explained by the use of different antibodies and techniques rather than true cellular differences and are reviewed here. This review summarizes the clinical relevance of uPAR and its soluble form in the prognosis and diagnosis of different cancers.