We aimed to evaluate the feasibility of sentinel lymph node biopsy (SLNB) in multicentric/ multifocal breast cancer. In this prospective study, 23 women with multicentric/multifocal breast cancer underwent SLNB at our institution from April 2002 to February 2006. Presence of preoperative axillary metastases was confirmed by FNA. Patients underwent sub-areolar radiopharmaceutical injection +/- isosulfan blue to perform SLNB, then completion ALND. The false-negative (FN) rate of SLNB was determined based upon final pathology. Twenty women with multicentric and three with multifocal invasive carcinoma were enrolled. The SLN identification rate was 100%. The overall FN rate of SLNB was 15% (95% CI 0.0466, 0.4281). Both cases with FN SLNB had multicentric disease, pathologic stage III breast cancer and a larger tumor burden compared with the study population. SLNB using sub-areolar injection is feasible for patients with multicentric/multifocal breast cancer yet may be associated with a higher FN rate in patients with large additive tumor burden.