Abstract: Gastric adenocarcinoma is the fourth most common cancer worldwide. Most cancers are sporadic, but in approximately 10% of the cases, familial aggregation is reported and a hereditary cause is detected in 1% to 3% of the cases. Several autosomal dominant inherited predispositions to cancer have been well described. Among them, gastric adenocarcinoma is the predominant manifestation of hereditary diffuse gastric cancer syndrome as well as gastric antral and proximal polyposis. Other syndromic condition associated with the development of gastric cancer includes familial adenomatous polyposis, Lynch syndrome, MUTYH-associated polyposis, Li-Fraumeni syndrome, BRCA1 and BRCA2 hereditary breast and ovarian cancer syndrome, and Peutz-Jeghers syndrome. In this review, we will focus on hereditary diffuse gastric cancer syndrome, which has been the subject of much scrutiny, but we will also offer a brief review of the cancer predisposition syndromes in which gastric adenocarcinoma may develop.