Background In the past decade, sentinel lymph node biopsy (SLNB) has become standard for patients with early-stage clinically node-negative breast carcinoma (BC). Despite high overall surgical identification success rates with introduction of the dual-tracer techniques (dye and radiolabeled probe), false-negative rates remained unchanged in most recent meta-analyses. Patients and Methods We analyzed cases with false-negative SLN biopsy results over a 12-year period in a single institution to evaluate their clinicopathologic characteristics. Sixty-three false-negative cases (3.1%) were found in 2043 successful SLN mapping procedures, all of which were followed by varying amounts of additional axillary sampling. Results There was a higher proportion of invasive lobular carcinomas (ILCs; 23 cases [37%]) when compared with this lesion's overall reported frequency (5%-15%). The majority of invasive ductal carcinoma (IDC) cases (31 of 40) were poorly differentiated. In 80% of the ductal-type cases, 1 or more nonsentinel nodes (NSLNs) were completely or partially replaced by tumor, as opposed to less than half of such cases of the lobular type. Twenty-two cases had multiple positive NSLN metastases, which were significantly associated with larger tumor size (≤1.0 cm) and tumor replacement of NSLNs. Eighty-two percent of the cases with known hormone receptor status were positive for estrogen or progesterone receptors, or both. Conclusion False-negative SLN biopsy results were more often associated with a primary BC characterized by a lobular or poorly differentiated ductal histologic type or partial to complete replacement of NSLNs with tumor, or both. © 2014 Elsevier Inc. All rights reserved.