BACKGROUND: Beyond the usual regimens based on streptozocin and doxorubicin or 5‐fluorouracil, no second‐line therapy of metastatic neuroendocrine tumor has gained wide acceptance. Gemcitabine and oxaliplatin are generally well tolerated and have shown activity against a wide range of malignancies. The authors assessed the efficacy of gemcitabine‐oxaliplatin combination (GEMOX) in the treatment of patients with metastatic neuroendocrine tumors. METHODS: Twenty consecutive patients with progressive disease were treated with GEMOX, in most cases after failure of other chemotherapy regimens (median = 2). Patients were followed for evidence of toxicity, response, and survival. Two patients were chemotherapy‐naive at treatment initiation and were excluded from the efficacy analysis. RESULTS: Toxicity was manageable overall; however, 6 (30%) patients had to discontinue treatment because of oxaliplatin‐induced neurotoxicity (grade 2). Three (17%) of 18 patients had a partial response, median progression‐free survival was 7.0 months, and median overall survival was 23.4 months. CONCLUSIONS: Gemcitabine‐oxaliplatin combination shows interesting activity and is well tolerated in pretreated patients with neuroendocrine tumors. Cancer 2009. © 2009 American Cancer Society.