Due to chemotherapy resistance and a high rate of relapse, triple negative cancers are among the most difficult breast cancers to treat. In this issue of the Journal of Clinical Investigation, researchers led by Carlos Arteaga at Vanderbilt University identified a protein, TGF-β, that is highly expressed in triple negative breast cancer cells after chemotherapy. In a mouse model of breast cancer, TGF-β both diverted cells down a path to becoming cancerous and allowed for cancer to come back after treatment. Importantly, loss of TGF-β prevented tumor recurrence in mice. These studies identify a mechanism by which cancer cells elude standard chemotherapy and provide a rationale for testing the therapeutic potential of agents that block TGF-β.