Cell adhesion is a key process, elementary in the establishment of tissue architecture and differentiation. In neoplasia, in which there is a disruption of tissue architecture and a derangement in differentiation, it has been postulated that changes in cell-cell and cell-matrix interactions account for the ability of cancer cells to transgress normal tissue boundaries and disperse to distant sites. Complex and coordinated reductions and increases in adhesion have been proposed to be necessary for tumor invasion and metastasis. This hypothesis has fueled the interest of cancer research teams to evaluate the expression of various adhesion molecules in a wide range of human malignancies in the hope of pinpointing some of the cell adhesion alterations underlying tumor behavior. To date, a multitude of transmembrane glycoproteins, including cell-cell adhesion molecules (CAMs) and cell-matrix or substratum adhesion molecules (SAMs), have been identified; their structure, molecular genetics, and biochemistry have been elucidated, and we are beginning to understand their normal function. A few of these, on the basis of current evidence, seem to be promising candidate molecules for a role in neoplasia. This article aims to summarize recent developments in this field of adhesion research as well as the clinical applications in diagnostic pathology arising from it. First, by way of introduction, a summary of the biochemical and functional characterization of each family of adhesion receptors will be presented, followed by a presentation of the experimental data implicating them in the control of invasion, metastasis, and differentiation.