10600 Background: Sentinel lymph node biopsy (SLNB), the preferred method of axillary staging in early breast cancer, is more sensitive and accurate compared to axillary node dissection. However, this data has not been incorporated into current prognostic models estimating the risk of breast cancer recurrence. We hypothesize that prognostic models based on data in the pre-SLN era underestimate survival and exaggerate benefits resulting from adjuvant therapy. In order to evaluate this hypothesis, we examined the disease free survival (DFS) and overall survival (OS) in an IRB approved, prospective, multicenter study of SLNB. Methods: From 1996–2005, 564 patients who had invasive disease in whom a SLN was found were examined from two experienced sites . Data was analyzed with regards to SLN status, tumor size, grade, lymphovascular invasion (LVI), age, estrogen receptor (ER) status and use of chemotherapy with respect to DFS and OS. Results: Median age was 57 years, tumor size was 1.5 (range 0.08–10.5) cm and follow-up was 46.2 (range 1–104.5) months. The SLN was positive in 31.2% of patients. The Kaplan-Meier (K-M) 5 year estimate of OS was 94.5(±1)% and DFS 88(±2)%. Tumor grade and size, LVI, ER- and +SLN significantly correlated with poorer DFS and OS by univariate analysis. By multivariate analysis, however, SLN status was the only statistically significant predictor for DFS (p = 0.004; HR = 3.4; CI = 1.5 - 8.0) and OS (p = 0.0051; HR = 7.3; CI = 1.8–29.4). SLN negative patients showed K-M 5 year DFS and OS estimates of 94(±)% and 97.4(±1)% respectively. There was no significant difference in DFS for SLN- patients treated with or without chemotherapy (p = 0.3). Conclusions: SLN status was the only significant predictor of DFS and OS. In node negative patients, we observed a higher DFS and OS than current statistical models based on historical data would have predicted. In this new era of SLNB, the magnitude of benefit from adjuvant therapy in sentinel node negative patients should be re-evaluated. No significant financial relationships to disclose.