Go online to PeerView.com/SMP860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. In the evolving era of precision cancer care, increasing emphasis is placed on detecting molecular alterations driving the development of specific cancers and targeting them with matched therapies or combinations that can yield the best outcomes for patients. Such is the case with HER2—and, more recently, also HER3 and TROP2—which are gaining growing interest as relevant targets in different malignancies. This is particularly important now, as a number of new targeted therapies have started to reach the clinic and are expected to change practice, and many others are showing great promise in clinical trials in breast, gastrointestinal, lung, and other tumors. Pathology professionals play an essential role in realizing the potential of precision cancer care by carrying out optimal predictive testing. This PeerView on-demand activity, based on a recent symposium at the United States and Canadian Academy of Pathology (USCAP) 108th Annual Meeting, features a panel of leading pathology and oncology experts, who share their insights into recent advances in testing and treatment of various HER2-altered cancers, including breast, gastrointestinal, lung, and other tumors. The emerging roles of HER3 and TROP2 as potential new targets are reviewed as well. In addition, they provide useful guidance to improve testing and best practices for interpretation, as well as interdisciplinary collaboration, all for the benefit of the patients. Upon completion of this activity, participants should be better able to: Review evidence-based guidelines and expert recommendations regarding HER2 testing and interpretation of results in breast, gastric, colorectal, non–small cell lung, and other cancers, Evaluate the characteristics, mechanisms of action, and efficacy/safety evidence of established and emerging HER2-targeted agents for the management of patients with advanced HER2-expressing or HER2-mutant cancers, Implement appropriate methods and best practices for HER2 testing and interpretation to guide integration of the latest HER2-targeted therapies into individualized treatment plans for patients with advanced HER2-expressing or HER2-mutant cancers either in the context of clinical practice or through clinical trial participation.