564 Background: With the increasing use of screening mammography, the proportion of ≤ 1 cm invasive breast cancer is increasing. Identification of breast cancer molecular subtypes has resulted in a better appreciation of the biologic heterogeneity, which is not fully explained by clinicopathologic features including staging system. The aims of this study were: 1) to identify the risk factors of systemic metastases in patients with ≤ 1 cm invasive breast cancer and 2) to investigate the patients group at greatest risk of such failure even in these small tumors. METHOD Data were collected retrospectively in the breast cancer registry of our institution for patients with invasive breast cancer from October 1994 to December 2004. RESULTS Of 4,036 patients who received curative breast cancer surgery, 466 patients who had T1a or T1b breast cancer were identified. 39 patients who received neoadjuvant chemotherapy were excluded in this study. Ipsilateral axillary lymph node involvement was found in 13% (57/427) at the time of surgery. Axillary lymph node involvement was much more common in HER-2 positive group (33% vs 11%, p < 0.0001) and triple negative (TN) group (24% vs 11%, p = 0.002) than in hormone receptor positive group. During median 61 months of follow-up, overall 10 year estimated distant relapse-free survival (DRFS) and overall survival (OS) were 95% and 92%, respectively. Multivariate analysis was conducted in 370 (T1aN0, T1bN0) patients, who had no lymph node involvement. In Cox-regression model, HER-2 positivity and triple negativity were identified as independent prognostic factors to predict DRFS [Hazard ratio (HR) 8.8, p = 0.003 for HER-2 positive group; HR 5.1, p = 0.026 for TN group] and OS (HR 5.0, p = 0.067 for HER-2 positive group; HR 11.1, p = 0.017 for TN group) in T1bN0 tumors. Limiting to T1aN0 tumors, statistical significance was not maintained. CONCLUSIONS Even though T1aN0 and T1bN0 tumors have been known to have a relative low risk of systemic failure, anti-HER-2 directed therapy for HER-2 positive group and new innovative adjuvant systemic treatment for TN group in patients with T1bN0 tumor should be considered. Prospective adjuvant trials should be warranted in these subgroups of patients. No significant financial relationships to disclose.