A 70-year-old woman was admitted with cervicomediastinal lymph node metastases from squamous cell carcinoma of unknown primary site (Sq-CUPS). The patient was treated with 4 cycles of chemotherapy combining carboplatin and paclitaxel with subsequent radiation therapy. After serial treatment, a partial response was obtained, and the disease has not recurred for over 2 years. Chemotherapy with carboplatin and paclitaxel followed by sequential radiation therapy was suggested to be potentially useful for Sq-CUPS with involvement of cervicomediastinal lymph nodes, although this group of patients is generally regarded to have a poor prognosis.