Although the current study could not provide sufficient evidence for HER2-directed therapy in these ERBB2-mutant metastatic EMPD tumors, anti-HER2 antibody–­drug conjugates should be considered, given the recent success of trastuzumab deruxtecan in ERBB2-mutant metastatic non-small-cell lung cancer, despite low HER2 protein expression levels. Here, ERBB2 is linked to extramammary Paget disease.