The ability of an epithelial cell to adhere to its neighbor and to the extracellular environment is an essential process that defines in part a normal multicellular organism. In the post-genomic era of cancer biology, it is known that epithelial tumors are multi-clonal and are genetically unstable. In contrast, during the process of tumor metastasis, which is the major cause of death from cancer, a restricted set of adhesion molecules are displayed on the tumor cell surface. The adhesion molecules provide a selective advantage for migration of the tumor cell to a distant site. In this volume, the expression of specific adhesion molecules within human cancer tissues are highlighted. The expression signatures from published DNA microarray and immunohistochemistry studies are detailed. The concept that the alteration of specific adhesion molecules influence the cancer migration ability and cancer damage responses is detailed in this volume; both features are essential for the survival of an invading tumor cell. Defining the minimal adhesion receptors preserved on cancer cells during tumor progression will define the metastatic adhesion signature. Understanding the metastatic adhesion signature will reveal vulnerabilities that could be exploited for the prevention and/or eradication of the invading cancer cell.