There is a growing body of evidence suggesting that alterations in the adhesion properties of neoplastic cells endow them with an invasive and migratory phenotype. Indeed, changes in the expression or function of cell adhesion molecules have been implicated in all steps of tumor progression, including detachment of tumor cells from the primary site, intravasation into the blood stream, extravasation into distant target organs, and formation of the secondary lesions. This review presents recent data regarding the role of cell adhesion molecules in tumor development and progress with concern to their clinical exploitation as potential biomarkers in neoplastic diseases.