No standard therapy exists for patients with metastatic melanoma whose disease failed to respond to first-line systemic treatment. We conducted a retrospective study to evaluate the clinical efficacy of the combination of docetaxel and temozolomide in previously treated patients. We searched our institution's patient and pharmacy databases for patients with metastatic melanoma who received docetaxel-tamozolomide and reviewed their medical records. We identified 38 patients who received docetaxel-temozolomide between February 2002 and January 2007 for resistant or refractory melanoma to a first-line therapy. The median age was 50 years, and all patients had stage IV melanoma (M1c, 87%) including 16 (42%) with brain metastases. All patients had received the same combination regimen: 80 mg/m docetaxel intravenously on day 1 and 150 mg/m temozolomide orally on days 1-5 every 28 days. Five patients (13%) had a partial response, and five (13%) had stable disease. The median time to disease progression was 8 weeks, and the overall survival duration was 26 weeks. Among the 10 patients who had a clinical benefit, the median time to disease progression was 51 weeks. Among 16 patients with brain metastases, none had confirmed clinical response in the brain. The regimen was generally well tolerated, with less than or equal to 8% of patients experiencing grade III or IV neutropenia or thrombocytopenia. Within the limitation of being a retrospective study with a potential patient selection bias, the docetaxel-temozolomide combination has modest activity, and is a reasonable option for previously treated patients with metastatic melanoma.