It is now widely recognized that alterations in the adhesion properties of neoplastic cells may play a pivotal role in the development and progression of the malignant phenotype in a range of tumor types. The cadherins and catenins, being the prime mediators of cell-cell adhesion, are intimately involved in the control of morphological differentiation and cellular proliferation; loss of their intercellular function allows malignant cells to escape from their site of origin, degrade the extracellular matrix, acquire a more motile and invasive phenotype, and, finally, invade and metastasize. In addition to participating in tumor invasiveness and metastasis, the E-cadherin-catenin complex is fundamental for the establishment and maintenance of multicellular organisms and regulates or significantly contributes to a variety of functions, including signal transduction, cell growth, differentiation, site-specific gene expression, morphogenesis, immunologic function, cell motility, wound healing, and inflammation. We reviewed the role of the E-cadherin-catenin complex in tumor development and presented the potential clinical applications of these molecules.