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The Laur\u00e9n classification system classifies GC under two major histopathological variants: 1) an intestinal type and 2) a diffuse type. The intestinal type is more common in the general population, more likely to be sporadic and related to environmental factors such as diet, particularly salted fish and meat as well as smoked foods, cigarette smoking, and alcohol use. It exhibits components of glandular, solid, or intestinal architecture, as well as tubular structures. On the other hand, the diffuse type is more likely to have a primary genetic etiology, a subset of which, known as hereditary diffuse gastric cancer (HDGC), is due to the <jats:italic>E\u2010cadherin (CDH1)<\/jats:italic> germline mutation. The diffuse type pathology is characterized by poorly cohesive clusters of cells which infiltrate the gastric wall, leading to its widespread thickening and rigidity of the gastric wall, known as linitis plastica. <jats:italic>Helicobacter pylori<\/jats:italic> infection is associated with risk for both the intestinal and diffuse varieties of gastric cancer. Germline truncating mutations of the <jats:italic>CDH1<\/jats:italic> gene, which codes for the E\u2010cadherin protein, were initially identified in three Maori families from New Zealand that were predisposed to diffuse GC. Since then, similar mutations have been described in more than 40 additional HDGC families of diverse ethnic backgrounds. It is noteworthy that two\u2010thirds of HDGC families reported to date have proved negative for the <jats:italic>CDH1<\/jats:italic> germline mutation. A number of candidate genes have been identified through analysis of the molecular biology of E\u2010cadherin. Patients with evidence of the <jats:italic>CDH1<\/jats:italic> germline mutation in the context of a family history of HDGC must be considered as candidates for prophylactic gastrectomy, given the extreme difficulty in its early diagnosis and its exceedingly poor prognosis when there is regional or distant spread. Specifically, the E\u2010cadherin cytoplasmic tail interacts with catenins, assembling the cell\u2010adhesion complex involved with E\u2010cadherin mediated cell:cell adhesion. \u03b2\u2010catenin and \u03b3\u2010catenin compete for the same binding site on the E\u2010cadherin cytoplasmic tail, directly linking the adhesion complex to the cytoskeleton through \u03b1\u2010catenin. \u03b2\u2010catenin gene (<jats:italic>CTNNB1<\/jats:italic>) mutations have been described predominantly in intestinal\u2010type gastric cancers and <jats:italic>CTNNB1<\/jats:italic> gene amplification and overexpression have recently been described in a mixed\u2010type gastric cancer. This paper reviews the genetics of both intestinal and diffuse types of gastric carcinoma, their differential diagnosis, molecular genetics, pathology, and, when known, their mode of genetic transmission within families. J. Surg. 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