E-cadherin is a form of cell adhesion molecule playing an important role in epithelial cell organization. Loss of function or loss of expression of this molecule due to mutations in the E-cadherin (CDH1) gene has been shown to be a key feature of the diffuse-type gastric adenocarcinoma. Of interest, in gastric adenocarcinoma showing a mixed diffuse and intestinal pattern, loss of E-cadherin is confined to the former component. In the breast, infiltrating lobular carcinoma, characterized by a diffuse permeative growth of neoplastic cells, has similarly been shown to exhibit loss of E-cadherin. Thus the molecular alteration (loss of E-cadherin) provides a plausible explanation for the observed morphologic phenotype of these two tumor types. Finally, rare families characterized by germline mutations in the E-cadherin gene have been shown to be strongly predisposed to the development of gastric cancer (diffuse-type) and/or infiltrating lobular carcinoma of the breast.