CDH1 on 16q22.1 encodes E-cadherin which functions in intercellular adhesion. E-cadherin is involved in transmitting chemical signals and controlling cell maturation and movement, and acts as a tumor suppressor. A lack of functional E-cadherin impairs cell adhesion and increases the likelihood of invasion and metastasis of tumor cells. More than 100 different pathogenic germline mutations are distributed throughout the CDH1 gene including splice-site sequences and have been found to cause a familial cancer disorder called hereditary diffuse gastric cancer (HDGC). Somatic CDH1 alterations are also found in approximately 30% of all patients with gastric cancers, both diffuse and intestinal types. CDH1 mutation identification in HDGC families is clinically important to assess the risk of gastric and breast cancers in unaffected relatives. Prognostic and therapeutic implications of this alterations remain to be fully elucidated. The 50 gene panel hotspot assay can not distinguish between germline or somatic(acquired) variants. Correlation with other clinical and lab findings, including genetic counseling, may be helpful, if clinically indicated.