Locally advanced breast cancer (LABC) has a poor prognosis with a high risk of local recurrence and distant metastasis. Preoperative combined chemotherapy with or without granulocyte colony-stimulating factor (G-CSF) support does not improve the long-term survival rate. In our report, two patients with LABC received preoperative high-dose chemotherapy with peripheral blood stem cell support (HDC/PBSCs). Prior to high-dose chemotherapy with peripheral blood stem cell support, they both received induction chemotherapy of cyclophosphamide, epirubicin and 5-fluorouracil (FEC) for two cycles which resulted in a partial response. PBSC mobilization and collection were carried out following the second cycle of induction chemotherapy followed by G-CSF. High-dose cyclophosphamide (2500 mg/m2), carboplatin (600 mg/m2) and etoposide (600 mg/m2) were administered with PBSC support. A radical mastectomy was performed followed by adjuvant chemotherapy with FEC regimen for four cycles, followed by local irradiation, and endocrine therapy with tamoxifen. Both patients achieved a remarkable response in the primary lesion after HDC/PBSCs and tolerated the whole treatment well. Preoperative HDC/PBSCs as a new strategy in the treatment of LABC seems practical but it needs to be studied more deeply.