BACKGROUND The current study was performed to evaluate the efficacy and toxicity of a noncisplatin‐based chemotherapy regimen combining gemcitabine and docetaxel as front‐line chemotherapy for patients with carcinoma of an unknown primary site. METHODS Patients were to receive intravenous gemcitabine at a dose of 1000 mg/m2 over 30 minutes on Days 1 and 8 and docetaxel at a dose of 75 mg/m2 over 1 hour on Day 8 in an outpatient setting. The schedule was repeated every 3 weeks for a maximum of 6 cycles. RESULTS Thirty‐five patients were assessable for response and survival. One complete and 13 partial responses were observed. The overall response rate was 40% (95% confidence interval, 28–52%). The median time to disease progression was 2 months (range, 1–4 months). The median overall survival time was 10 months (range, 0–32 months). Toxicity was reported to be manageable. CONCLUSIONS The combination of gemcitabine and docetaxel was found to be active in patients with carcinomas of an unknown primary site. However, the overall outcome of these patients remains poor and novel treatment approaches are required. Cancer 2004. © 2004 American Cancer Society. A median survival of 10 months was observed in 36 patients with carcinomas of an unknown primary site who were treated with a noncisplatin‐based chemotherapy regimen combining gemcitabine and docetaxel.