Gastric cancer is one of the most prevalent and fatal in the world, especially due to its invasive nature, and the capacity to metastasize at distance, frequently without symptoms. E-cadherin is one of the most important structural molecules in the stomach, and its expression in the gastric epithelia suppresses cancer development. Carriers of mutations in the gene encoding E-cadherin have high probability of developing hereditary diffuse gastric cancer. Strategies aiming to prevent the loss of E-cadherin expression enclose high therapeutic potential for gastric cancer.