We evaluated the survival benefit, safety, feasibility, and tolerability of dose-dense (DD) adjuvant chemotherapy with epirubicin and paclitaxel for women with node-positive primary breast cancer. Randomised patients (n=216) received DD or conventional-schedule (CS) chemotherapy. Dose-dense regimen patients (n=108) received epirubicin 90 mg m-2 plus paclitaxel 175 mg m-2 in four 14-day cycles, then cyclophosphamide 600 mg m-2, methotrexate 40 mg m-2, and fluorouracil 600 mg m-2 (CMF 600/40/600) in three 14-day cycles, plus filgrastim 5 microg kg day-1 as growth support in every cycle. Conventional-schedule regimen patients (n=108) received epirubicin 90 mg m-2 plus cyclophosphamide 600 mg m-2 in four 21-day cycles, then CMF 600/40/600 in three 21-day cycles, plus filgrastim if required. After a median follow-up of 38.4 months, 71 patients (33%) relapsed or died: DD, 33 patients (15 deaths); CS, 38 patients (22 deaths). Dose dense showed a trend for improved disease-free survival (DFS) and overall survival (OS). Four-year rates of DFS and OS were 64 and 85% for DD, and 58 and 75% for CS. All seven cycles were administered to 208 patients (96%). Rates of cycle delay, discontinuation, dose reduction, and adverse events were similar in both groups. Dose-dense sequential chemotherapy with epirubicin/paclitaxel then CMF, supported by filgrastim, is safe and improves survival for patients with node-positive breast cancer.