A 77-year-old woman visited our hospital with the chief complaint of left supraclavicular lymph node redness and swelling. Needle biopsy revealed metastatic, epithelial, undifferentiated carcinoma. However, the primary tumor remained unknown despite further thorough examinations, FDG-PET showed abnormal FDG accumulation at the lymph nodes of para-aortic and left external iliac artery area in addition to left supraclavicular lymph node. However, CT and MRI showed no lymph node swelling in the peritoneal cavity. Nedaplatin (CDGP) combined with S-1 therapy was carried out for this primary unknown cancer with lymph node metastases. Three months after CDGP/S-1 therapy was begun, the swollen left supraclavicular lymph node was obviously reduced by 42.5%. Moreover, abnormal FDG accumulation at left supraclavicular and para-aortic lymph nodes dramatically decreased and that at the left external iliac artery area disappeared. The anti-tumor effect was evaluated as a partial response by use of Response Evaluation Criteria in Solid Tumors (RECIST). Standard treatment for primary unknown cancer was not established, because it includes various carcinomas. Here we report a case of primary unknown cancer successfully treated with CDGP/S-1. This combined therapy was considered to be one of the promising strategies for a primary unknown cancer.