We report a 49-year-old Chinese male with locally advanced gastric adenocarcinoma achieving pathological complete response after neoadjuvant chemotherapy with trastuzumab-containing regimen. He underwent esophagogastroduodenoscopy in September 2009, which revealed a 2-cm gastric ulcer on the lesser curvature proximal to angularis. Biopsy of gastric ulcer showed moderately differentiated adenocarcinoma with overexpression of human epidermal growth factor receptor 2 (HER2) by immunohistochemistry and fluorescence in situ hybridization. Further workups with endoscopic ultrasound, computed tomography and positron emission tomography staged his cancer as T3N1M0. He received 3 cycles of neoadjuvant chemotherapy consisting of trastuzumab, oxaliplatin, docetaxel and capecitabine without severe toxicities except grade 2 diarrhea near the completion of cycle 3 requiring discontinuation of capecitabine. Afterwards, he received total gastrectomy with extended D2 lymph node dissections showing pathological complete response. He went on to receive 3 more cycles of chemotherapy postoperatively. The role of trastuzumab as a part of perioperative therapy in gastric cancer overexpressing HER2 is worth further investigation.