Patients with metastatic breast cancer (MBC) are increasingly offered third line chemotherapy. We have reviewed the response rate (RR), time to progression (TTP) and survival of 149 patients in this setting and have investigated factors that influence their outcome. The RR, TTP and survival were 30%, 4 and 8 months, respectively, and should serve as a benchmark for future studies. Response to previous chemotherapy was the only independent variable predicting RR, TTP and survival, p=0.025, 0.04 and 0.004, respectively. Thirty-two percent of patients did not respond to the first two lines of chemotherapy and had a lower RR and a significantly shorter TTP and survival. In conclusion, third line chemotherapy for MBC is sometimes effective in patients who have responded to previous chemotherapy. Patients who do not respond to the first two lines of chemotherapy should be considered for clinical trials or supportive care.