Daniel Catenacci, MD, University of Chicago, Chicago, IL, discusses the clinical implications of HER2 in gastrointestinal cancers as discussed at the American Society of Clinical Oncology (ASCO) 2021 Virtual Meeting and highlights the role of HER2-targeted agents in gastroesophageal cancer as well as molecular heterogeneity in HER2 expression seen in gastrointestinal tumours which may result in differences in response to HER2 agents. This interview took place at the American Society of Clinical Oncology (ASCO) 2021 Virtual Meeting.