A triad of TLR3 stimulation, NF-κB and β-catenin activities in promoting CSC phenotypes indicates a combinational use of TLR3 agonists with NF-κB and β-catenin inhibitors, but neither alone, may help to improve clinic outcomes and efficacy of TLR3 agonists in patients with breast cancer. The gene discussed is TLR3; the disease is breast cancer.