Additional benefit of trastuzumab was revealed as a primary treatment for advanced gastric cancer with HER2-positive by ToGA trial. The treatment of second-line treatment for patients with primary refractory is unknown, however. There are many questions, such as seroconverted during the course of treatment of false-negative cases. It can be expected that the earliest second-line HER2-positive gastric cancer is Lapatinib, a tyrosine kinase inhibitor of both HER2 and EGFR. On the other hand, numerous clinical trials related to ‘Beyond Progression’ of additional benefit for continuing trastuzumab is conducting in many Oncology Group. HER2-positive gastric cancer is limited and coordination with each group efficiently is needed. In conducting clinical trials, it would be more important to manage the collection and analysis of serum and tissues samples for the purpose of biomarker study.