Morphogenesis is the process by which cells become organized into distinctive structures and histological patterns in the tissues and organs of the body. Cellular morphogenetic mechanisms operate to establish tissue architectures during embryonic life, and also maintain tissue organization after birth. Cancer, particularly the clinically aggressive phases of tissue invasion and metastasis, is characterized by fundamental disturbances in this orderly patterning of cells within tissues. In seeking to understand the cellular basis of cancer, it has therefore been attractive to postulate that aberrant morphogenetic processes may play fundamental roles in tumor biology. There is, indeed, increasing evidence to support this hypothesis. The purpose of this review is to discuss one such line of evidence: the ways in which disturbances in cadherin-based cell adhesion contribute to tumor progression in a range of epithelial tumors. Because this burgeoning research industry has been the subject of several recent comprehensive reviews (1, 2), I will aim to give a thematic overview, with a particular focus on ways in which the physiological role of cadherins in morphogenesis may-e coopted or pertui-ed in cancer to generate an invasive and metastatic phenotype. Cell adhesion is a fundamental determinant of tissue morphogenesis (3, 4). The cadherins comprise a large superfamily of cell-surface glycoproteins, which have in common a repeated 1 10-amino-acid subdomain (called the “cadherin” domain) in their extracellular region (3). Cadherins mediate cell-cell adhesion in all solid tissues of the body (3, 4). Of these glycoproteins, E-cadherin is found in most epithelial tissues and is among the best understood of the cadherins. Studies using cell culture have shown that E-cadherin is necessary for many aspects of epithelial morphogenesis, including cell cohesion and junctional assembly (reviewed in Refs. 1, 4, 5). Targeted deletion of the E-cadherin gene in mice resulted in embryonic lethality due to failure of the blastoderm, the first primitive epithelium, to form (6), whereas tissue-specific expression of dominant-negative cadherin mutants showed that E-cadherin was necessary for integrity of the small-intestinal epithelium (7). E-cadherin therefore plays a central role in epithelial morphogenesis. Importantly, the vast majority of evidence implicating cadherins in human cancer involves abnor-