Anti-HER2 therapy has recently emerged as an effective targeted treatment approach for patients with advanced stage and recurrent endometrial serous carcinoma, resulting in significantly prolonged progression-free and overall survival when combined with the standard chemotherapy regimen. Consequently, there is an increasing clinical demand in pathology laboratories for HER2 testing of these tumors. This article provides an overview of the unique characteristics of HER2 protein expression and gene amplification in endometrial serous carcinoma and summarizes the HER2 scoring criteria used for patient enrollment in the recent clinical trial. Following the experience of guideline-development in other tumor types, the trial criteria should serve as the basis for future endometrial carcinoma-specific HER2 testing and scoring recommendations, to ensure therapeutic response in new patient cohorts. Thus, based on the clinical trial, the author proposes a specific HER2 testing algorithm for endometrial serous carcinoma to guide the current clinical practice. Future studies are necessary to refine and adjust these criteria to allow for appropriate triaging of patients and maximize the clinical benefit from HER2-targeted therapy.