ABSTRACT Introduction Perioperative adjuvant treatment for esophagogastric junction adenocarcinoma has been attempted, but efficacy of preoperative therapy is unclear. We report here a case of pathological complete response after preoperative treatment containing trastuzumab in esophagogastric junction adenocarcinoma. Case presentation A 54-year-old man presented at our institute with dysphagia. Esophagogastroduodenoscopy and computed tomography revealed an 8 x 5 cm-sized tumor on the gastric cardia and lower intrathoracic esophagus with invasion to the diaphragm (T4bN0M0, StageIIIB). Biopsy showed a well-differentiated and human epidermal growth factor receptor 2-positive adenocarcinoma. He received 2 cycles of preoperative chemotherapy consisting of trastuzumab, cisplatin, and capecitabine without severe toxicity. Afterwards, he underwent esophagectomy and total gastrectomy with mediastinal and abdominal D2 lymph node dissections. No cancer cells were detected during histopathological examination, indicating pathological complete response. Conclusion Regimens containing trastuzumab are feasible and promising as preoperative chemotherapy for human epidermal growth factor receptor 2-positive esophagogastric junction adenocarcinoma.