Trastuzumab, a humanized monoclonal antibody against human epidermal growth factor receptor 2 (HER2), has been proven to result in a survival benefit for the treatment of patients with HER2-positive advanced gastric cancer (AGC). However, data are lacking for the treatment of those with disseminated intravascular coagulation (DIC) and diffuse bone marrow carcinomatosis. A 77-year-old woman presented with back pain and fatigue since 2 months. Esophagogastroduodenoscopy showed a scirrhous lesion in the gastric corpus, which was biopsied and identified as signet-ring cell carcinoma with HER2 overexpression on immunohistochemistry. Laboratory testing, bone scintigraphy, and bone marrow biopsy were conducted, and she was diagnosed with HER2-positive AGC with DIC and diffuse bone marrow carcinomatosis. She underwent chemotherapy with the following regimen: oral administration of 80 mg/m2 S-1 for 2 weeks and 6 mg/kg trastuzumab infusion on day 6 every 3 weeks, which significantly improved the DIC. She was discharged from the hospital 73 days after admission and survived for 438 days after diagnosis. To the best of our knowledge, this is the first case report in which HER2-positive AGC complicated by DIC with diffuse bone marrow carcinomatosis was successfully treated with combined chemotherapy consisting of S-1 plus trastuzumab.