PURPOSE: As 5-fluorouracil (5-FU) has previously exhibited antitumor activity and few adverse effects in the treatment of breast cancer, we aimed to specifically assess the benefits of orally administered 5-FU in hormone receptor-negative small breast cancer. METHODS: We retrospectively identified patients with pT1aN0 and hormone receptor-negative breast cancer who underwent surgery between 1993 and 2008 at Asan Medical Center. Patients were divided into two cohorts based on adjuvant doxifluridine (Didox; Shin Poong Pharm. Co., Ltd.) administration, and the disease-free survival (DFS) and cancer-specific survival (CSS) was assessed for each cohort. RESULTS: Both cohorts had similar ages and tumor sizes. The DFS and CSS did not significantly differ between the groups (p=0.399 and p=0.126, respectively). When the cohorts were assessed according to human epidermal growth factor receptor 2 (HER2) status, doxifluridine significantly improved DFS among patients with T1aN0 and HER2-positive breast cancer (p=0.037). CONCLUSION: Doxifluridine did not yield a significant reduction in DFS events in hormone receptor-negative early breast cancer. However, a clear benefit was observed in hormone receptor-negative, HER2-positive T1aN0 breast cancer patients.