The role of cadherins in cutaneous biology has focused mainly on the classical cadherins, E- and P-cadherin. In this review, roles for cadherins in skin morphogenesis, keratinocyte differentiation, and cancer metastasis are discussed. E-cadherin is expressed on the surfaces of whole epidermal layer cells, and P-cadherin is expressed only on the surfaces of basal cells. Ultrastructural studies have shown that E-cadherin is distributed on the cytoplasmic membranes of keratinocytes with a condensation in the intercellular space of the desmosomes. During human skin development, P-cadherin expression is spatiotemporally controlled and closely related to the segregation of basal layers as well as to the arrangement of epidermal cells into eccrine ducts. In human skin diseases, E-cadherin expression is markedly reduced on the acantholytic cells of tissues in pemphigus and also in Darier's disease. Keratinocytes cultured in high calcium produce a much more intense immunofluorescence of intercellular E- and P-cadherin than do cells grown in low calcium. Ultrastructural studies show that E-cadherin on the cytoplasmic membrane of the keratinocytes is shifted to desmosomes under physiological conditions and therein expresses an adhesion function is association with other desmosomal cadherins. Cell adhesion molecules are now considered to play significant roles in the cellular connections of cancers and metastatic cells. Reduced expression of E-cadherin on invasive neoplastic cells has been demonstrated for cancers of the stomach, liver, breast, and several other organs. This reduced expression of E-cadherin is observed in squamous cell carcinoma and Paget's disease. Soluble E-cadherins in sera are elevated in various skin diseases, including bullous pemphigoid, pemphigus vulgaris and psoriasis, but not in patients with burns. Markedly high levels in soluble E-cadherin are demonstrated in patients with metastatic cancers.