The purpose of this study was to evaluate pathologic complete response (pCR) rates and adverse events with primary systemic therapy (PST) of intermittent weekly paclitaxel and gemcitabine in patients with stage II and III breast cancer. Node-positive patients with stage II and III breast cancer received paclitaxel 80 mg/m(2) followed by gemcitabine 1,200 mg/m(2) on day 1 and day 8, every 3 weeks for four cycles. Postoperatively, four cycles of doxorubicin 60 mg/m(2) and cyclophosphamide 600 mg/m(2) every 3 weeks were given. Of 44 enrolled patients, 73% had stage III breast cancer with 68% hormone-receptor positive and 41% HER2 positive tumors. Eight patients achieved pCR in primary tumors (18%), 11 in axillary nodes (25%), and five in both tumor and axillary nodes (11%). Breast conservation was possible in 28 patients (64%). Grade III/IV toxicities were neutropenia (57%), leukopenia (14%), febrile neutropenia (2%), and headache (2%). In conclusion, PST with intermittent weekly paclitaxel and gemcitabine in patients with stage II/III breast cancer is both well tolerated and effective, showing 18% pCR rate in the breast.