ObjectivesThis study examined the accuracy of radioactive seed localization (RSL) of lymph nodes (LNs) following neoadjuvant chemotherapy (NAC) for invasive breast carcinoma, recorded pathologic features of LNs following NAC, evaluated concordance of response between breast and LNs, and identified clinicopathologic factors associated with higher risk of residual lymph node involvement.MethodsClinical records, imaging, and pathology reports and slides were retrospectively reviewed for 174 breast cancer patients who received NAC. Chi-square and Fisher’s exact tests were used to compare differences in risk of residual lymph node disease.ResultsRetrieval of biopsied pre-therapy positive LN was confirmed in 86/93 (88%) cases overall, and in 75/77 (97%) of cases utilizing RSL. Biopsy clip site was the best pathologic feature to confirm retrieval of a biopsied lymph node. Pre-therapy clinical N stage > 0, positive pre-therapy lymph node biopsy, estrogen and progesterone receptor positivity, Ki67 < 50%, HR + /HER2− tumors, and residual breast disease had higher likelihood of residual lymph node disease after NAC (p< 0.001).ConclusionsRSL-guided LN excision improves retrieval of previously biopsied LNs following NAC. The pathologist can use histologic features to confirm retrieval of targeted LNs, and tumor characteristics can be used to predict a higher risk of residual LN involvement.