There is no standard treatment for breast cancer patients whose tumors have been exposed both to anthracyclines and taxanes. Oxaliplatin shows synergism with 5-fluorouracil (5-FU) and capecitabine is an oral prodrug of 5-FU with known efficacy in pretreated patients. This phase II trial studied the efficacy and toxicity of the oxaliplatin-capecitabine combination as salvage treatment in breast cancer patients pretreated with anthracyclines and taxanes. Patients received oxaliplatin 80 mg/m(2) on day 1 followed by oral capecitabine 1800 mg/m(2) divided in two doses for 7 days every two weeks for a maximum of twelve courses or until disease progression. Twenty-eight patients were evaluable for efficacy and toxicity. Objective responses (all partial) were documented in 9 patients [32%; 95% confidence interval (CI): 13-51.2%]. Responses were documented at all metastatic sites. The median response duration was 5 months (range 3-9), median time to progression was 4.5 months (range 2-10) and median overall survival was 10 months (range 2-18). Myelotoxicity was minimal with grade 3 thrombocytopenia as the main toxicity. Hand-foot syndrome was well tolerated. The present regimen was well tolerated with a rather moderate effectiveness but very significant for this group of patients. Further studies where the combination could be compared with single agent capecitabine are warranted.