Hereditary diffuse gastric cancer (HDGC) is an autosomal dominant form of diffuse gastric cancer that is associated with sequence variants in the cadherin 1, type 1, E-cadherin (epithelial) (CDH1) gene. It is estimated that, in 2010, 21,000 individuals will be diagnosed with gastric cancer and 10,570 will die from the disease in the United States. If diagnosed when localized, gastric cancer may be successfully treated in 50% of patients, but for the 80% to 90% of gastric cancers that are identified at more advanced stages, the 5-year survival rate is typically 10% to 15%. Gastric cancer usually occurs sporadically, with approximately 10% being familial and 1% to 3% hereditary. The prevalence of HDGC has not been accurately defined, but it occurs predominately in European populations. The mean age of onset of HDGC is 38 years. In addition to gastric cancer, HDGC is also associated with an increased risk of lobular breast cancer in women. For symptomatic patients, management of HDGC is through total gastrectomy followed by combined chemoradiation therapy. For asymptomatic individuals at risk of HDGC, management is by twice-yearly endoscopic surveillance or prophylactic gastrectomy. As a result of the diffuse nature of HDGC it is difficult to observe endoscopically. Gastrectomy is associated with morbidity, including postoperative complications, rapid intestinal transit, dumping syndrome, diarrhea, weight loss, and risk of longterm metabolic complications; and a 1% to 4% chance of mortality.