Advanced Extramammary Paget’s disease (AEMPD) shows a poor prognosis despite multimodality therapy. In recent years, it is suggested that anti-HER2 therapy may be promising for HER2-positive AEMPD. We herein present an autopsy case of a patient with AEMPD treated with multimodality treatment including anti-HER2 therapy. A 78-year-old man who diagnosed with AEMPD died after surgery and systemic chemotherapy including anti-HER2 therapy (trastuzumab). The metastatic skin lesions were immnohistologically HER2-positive. While the patients were administrated trastuzumab plus taxan (docetaxel, and paclitaxel) regimen, the metastatic skin lesion decreased, however, brain metastases were found in his brain and trastuzumab is discontinued. The skin metastasis rapidly spread over his body, leading to weakness, and he eventually died. At autopsy, the lesions of EMPD were extended distant organs including brain, although each metastasis was small and asymptomatic. The wide lesion of skin metastasis was exacerbated after discontinuation of trastuzumab, and transudate was observed due to the extensive necrosis and erosion. Our autopsy findings showed one progressive pattern of AEMPD, and indicated what is the clinical and pathological significance of anti HER2 therapy for HER2-positive AEMPD.