An 83-year-old woman was diagnosed as having advanced gastric cancer with multiple lymph node and hepatic metastases. Histopathological examination revealed that the tissue was human epidermal growth factor receptor 2(HER2)positive. The patient underwent gastrojejunostomy to improve stomach obstruction. Thereafter, S-1 and trastuzumab combination chemotherapy was administered as first-line treatment; irinotecan(CPT-11), cisplatin, and trastuzumab combination chemotherapy, as second-line treatment; and docetaxel plus trastuzumab combination chemotherapy, as third-line treatment. Although both primary and metastatic lesions decreased in size temporarily, their size increased again, and the patient died 1 year and 7 months later. The level of serum HER2-extracellular domain(ECD)was a valuable indicator of response to chemotherapy. Thus, serum HER2-ECD could be a useful biomarker for HER2-positive gastric cancer.