BackgroundRepeat sentinel lymph node biopsy (rSLNB) has increasingly been used in patients with ipsilateral breast tumor recurrence (IBTR). The safety in terms of regional disease control after this procedure remains unclear. This study evaluates occurrence of regional recurrence as first event in patients with IBTR and negative rSLNB, treated without additional lymph node dissection.Patients and MethodsData were obtained from the Sentinel Node and Recurrent Breast Cancer (SNARB) study. In 201 patients, tumor-negative rSLNB was obtained without performing additional lymph node dissections.ResultsWith median follow-up of 4.7 (range 0.9–12.7) years, regional recurrence occurred after median time of 3.0 (range 0.4–6.7) years in 4.5% (N = 9) of patients as first event after IBTR and rSLNB. In four of these nine patients, the site of recurrence was in concordance with the anatomical location of rSLNB. Two of the nine recurrences were reported in the ipsilateral axilla, resulting in an ipsilateral axillary regional recurrence rate of 1.0%. In the other seven patients, regional recurrence occurred in aberrant basins. Univariable analysis showed that triple-negative IBTR and lower amount of radioactive-labeled tracer (99mtechnetium) used during rSLNB were associated with developing regional recurrence as first event after negative rSLNB (P < 0.05).ConclusionsThe risk of developing regional recurrence after negative rSLNB is low. The low relapse rate supports the safety of rSLNB as primary nodal staging tool in IBTR. The time has come for clinical guidelines to adopt rSLNB as axillary staging tool in patients with IBTR.Electronic supplementary materialThe online version of this article (10.1245/s10434-018-6384-y) contains supplementary material, which is available to authorized users.