The standard first-line treatment of recurrent/metastatic head and neck squamous cell carcinoma is cisplatin-based chemotherapy, but taxanes can also be beneficial after progression or in patients not eligible for cisplatin. The objective of this retrospective study was to evaluate paclitaxel in this population. We reviewed 66 patients who were treated with paclitaxel at a single institution (Lyon, France) between January 2003 and November 2008. Paclitaxel was administered as first, second or more line of treatment; alone or in combination with carboplatin or cetuximab; every 3 weeks (175 mg/m(2)) or weekly (80 mg/m(2)). Forty-six (70%) patients received paclitaxel as first-line therapy after relapse and 26 (39%) patients as monotherapy. The objective response rate was 30% [95% confidence interval (CI): 20-43%]; 37% (95% CI: 23-52%) in the first line after relapse, and 20% (95% CI: 4-48%) in the second line. Rates were 19% (95% CI: 7-39%) after monotherapy and 36% (95% CI: 20-55%) after combination with carboplatin. Two of the six patients receiving cetuximab had a partial response. The overall survival of all patients was 7.2 months (95% CI: 5.2-8.8). Paclitaxel can be used in symptomatic patients. Although no improvement of overall survival can be expected, paclitaxel treatment is safe and achieves interesting response rates.