Gastric mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) is an extremely rare form of gastric neoplasm, and its prognosis is often poor. This is a case report wherein the primary site increased during chemotherapy against gastric adenocarcinoma and was diagnosed with gastric MiNEN after total gastrectomy. A 71-year-old man was diagnosed with gastric adenocarcinoma complicated with liver and para-aortic lymph node metastasis. Chemotherapy with S-1, oxaliplatin, and trastuzumab was initiated. Although the size of metastatic lesions was reduced after six courses of treatment, a part of the primary site of gastric tumor rapidly. Pathological rebiopsy of the primary site suggested a neuroendocrine carcinoma, and he was finally diagnosed with gastric MiNEN after total gastrectomy. Thus, second-line chemotherapy was then initiated showing good response. We herein report a case of MiNEN with a rare diagnostic process.