BACKGROUND: American College of Surgeons Oncology Group Z0010 is a prospective multicenter trial designed to evaluate the prognostic significance of micrometastases in the sentinel lymph nodes and bone marrow aspirates of women with early-stage breast cancer. Surgical complications associated with the sentinel lymph node biopsy surgical procedure are reported. METHODS: Eligible patients included women with clinical T1/2N0M0 breast cancer. Surgical outcomes were available at 30 days and 6 months after surgery for 5327 patients. Patients who had a failed sentinel node mapping (n=71, 1.4%) or a completion lymph node dissection (n=814, 15%) were excluded. Univariate and multivariate analyses were performed to identify predictors for the measured surgical complications. RESULTS: In patients who received isosulfan blue dye alone (n=783) or a combination of blue dye and radiocolloid (n=4192), anaphylaxis was reported in .1% of subjects (5 of 4975). Other complications included axillary wound infection in 1.0%, axillary seroma in 7.1%, and axillary hematoma in 1.4% of subjects. Only increasing age and an increasing number of sentinel lymph nodes removed were significantly associated with an increasing incidence of axillary seroma. At 6 months, 8.6% of patients reported axillary paresthesias, 3.8% had a decreased upper extremity range of motion, and 6.9% demonstrated proximal upper extremity lymphedema (change from baseline arm circumference of >2 cm). Significant predictors for surgical complications at 6 months were a decreasing age for axillary paresthesias and increasing body mass index and increasing age for upper extremity lymphedema. CONCLUSIONS: This study provides a prospective assessment of the sentinel lymph node biopsy procedure, as performed by a wide range of surgeons, demonstrating a low complication rate.