Sentinel lymphadenectomy is a sensitive and specific procedure that has reduced the need for complete axillary lymph node dissections in patients with negative sentinel lymph nodes (SLNs). However, numerous studies have shown that SLN may be the only positive lymph node in 40 to 70% of cases. This study was therefore undertaken to determine if the characteristics of primary breast tumor or its metastasis in the SLN could predict the presence of residual disease in the nonsentinel lymph nodes (NSLNs) and thus allow for further reduction in axillary lymph node surgery. The SLN procedure was performed on 329 patients at our institution, of which 131 had positive SLNs and underwent further axillary surgery. Fifty-four patients had additional disease in the NSLNs, while in the remaining 77 cases, no residual disease was detected. The clinical and pathologic features of these cases were reviewed and statistical analysis was performed. Multivariate analysis determined two significant independent variables for prediction of residual disease in the axilla: the size of the metastatic tumor in SLNs and the presence of its extranodal extension. The mean tumor size in SLNs without residual disease in NSLNs was 0.4 cm. It was 1.1 cm in patients with additional NSLN metastasis. The positive predictive value in both instances is about 80%. The risk of NSLN involvement in patients with SLN tumors of < or = 0.4 cm was 21%. The risk was the same (21%) for patients with micrometastatic disease (< or = 0.2 cm) in SLNs. In these cases the residual disease in the NSLNs was also small. SLNs with metastatic deposits larger than 1.0 cm were likely to contain additional metastases in the NSLNs in 81% of cases. This increased to 100% if the primary carcinoma was larger than 5 cm, if it was poorly differentiated, or if it showed HER-2/neu gene amplification. The presence of an extranodal extension of SLN metastasis was an independent predictor of residual axillary disease and was associated with NSLN metastasis in 76% of cases. Primary tumor characteristics did not correlate with the incidence of NSLN metastasis in our series.