We found that ZFHX3 promotes breast cancer cell proliferation and tumor growth, and the underlying cellular and molecular mechanisms involve BCSC-like features and transcriptional activation of MYC and TBX3. These findings suggest a regulatory role of ZFHX3 in breast carcinogenesis and provide a potential therapeutic opportunity for breast cancer therapy. The gene discussed is ZFHX3; the disease is breast carcinoma.