Trop2 is a cell-surface glycoprotein reported to be overexpressed in various types of adenocarcinomas with minimal expression in normal tissues. Recent findings that Trop2 expression correlates with tumor aggressiveness have increased interest in Trop2 as a potential target for cancer immunotherapy. The goal of this study was to extensively evaluate Trop2 expression at the transcript and protein levels in normal and tumor tissues. It was determined that Trop2 is overexpressed on some carcinomas relative to the corresponding normal tissue. However, in human and mouse, Trop2 is highly expressed at both the transcript and protein levels on several essential normal tissues. The findings suggest that the development of therapeutic agents to target Trop2 may require strategies that target Trop2 on malignant tissues in order to minimize potential toxicities to essential normal tissues that also express high levels of Trop2.