Hereditary gastric cancer is an autosomal-dominant inherited condition produced by germline mutation in the E-cadherin/CDH1 gene. Criteria to define the syndrome have been proposed and include review of the histopathology and pedigree analysis of any family with an aggregation of gastric cancer cases. Of families with two or more cases of diffuse gastric cancer in first- or second-degree relatives aged < 50 years or three or more cases of relatives at any age, up to one half may be attributable to inherited germline mutations in the E-cadherin/CDH1 gene. The cumulative lifetime risk of developing gastric cancer in CDH1 mutation carriers is > 70% and women from these families also have an increased risk for developing lobular breast cancer. Prophylactic gastrectomy has been performed in several unaffected CDH1 mutation carriers, and despite normal endoscopic examinations and negative gastric biopsy specimens, pathologic foci of early gastric cancer were found in the vast majority of surgical specimens. Based on these results, guidelines for genetic testing, counseling, and management of individuals with hereditary diffuse gastric cancer are suggested. Raised awareness among the physician community regarding this syndrome may allow for increased detection and prevention of gastric and breast cancers in these high-risk individuals.