Docetaxel is one of the most active cytotoxic drugs against breast cancer, but data are lacking on specific activity in molecularly selected subgroups. This retrospective study was aimed at assessing the outcome and prognostic factors for survival of patients with HER2-negative tumors receiving first-line docetaxel-based chemotherapy for advanced breast cancer (ABC). The medical charts of all 162 patients with prospectively proven HER2-negative ABC and having received docetaxel as first-line chemotherapy for metastatic disease at our institution were retrospectively reviewed with special emphasis on docetaxel efficacy. Potential prognostic factors were sought using multivariate analysis. Median progression-free survival (PFS) was 12 months (95% confidence interval 9.7-14.8) and median overall survival (OS) was 34.9 months (95% confidence interval 28.1-52.1). Hormone receptor (HR) status was the strongest prognostic factor in the univariate analysis for both PFS [hazard ratio = 0.23; P = 0.00000063] and OS (hazard ratio = 0.35; P = 0.0000079). After multivariate analysis, only three independent variables for PFS (HR-positive tumor, no prior adjuvant/neoadjuvant chemotherapy, and isolated bone metastases) and two for OS (HR-positive tumor and isolated bone metastases) remained predictive of a favorable outcome. HER2-negative, HR-positive ABC patients have a relatively good prognostic after docetaxel-containing first-line therapy. The subset of HER2-negative, HR-negative (triple-negative) has a very poor outcome, and innovative therapies are eagerly awaited for these patients.