Amplification of the human epidermal growth factor receptor 2/neu (HER2/neu) gene and overexpression of the HER2 protein (HER2) have been shown to occur in gastric and gastroesophageal junction adenocarcinoma in a number of studies. With a dismal survival rate, patients with these cancers stand to benefit from the identification of possible molecular targets such as HER2 for both prognostic and therapeutic purposes. Although these and other carcinomas that overexpress HER2 may have a poorer prognosis and exhibit resistance to conventional chemotherapy, they have also recently been shown to respond to targeted therapy with the anti-HER2 antibody trastuzumab. Here, we briefly review the molecular biology, histopathology, diagnostic techniques, and interpretation, as well as the clinical implications, of HER2 amplification/overexpression in gastric and gastroesophageal adenocarcinoma.