Background: Sentinel lymph node biopsy (SLNB)-guided axillary management is still debated for clinically node-positive breast cancer (BC) patients treated with neoadjuvant chemotherapy (NAC). Several phase II studies demonstrated high false-negative rates (FNR) in ycN0 BC, but precise diagnostic imaging for nodal involvement may reduce FNR. To explore ideal imaging and lymphatic mapping, the Japanese Society for Sentinel Node Navigation Surgery conducted a prospective non-randomized phase 2 study (SHARE study, UMIN000030558). Methods: Clinical T1-3N1M0 BC was eligible under multimodal imaging of breast ultrasound, CT and/or MR mammography. Nodal metastasis was histologically confirmed. Standard regimen for NAC was performed by physician’s choice. In case of ycN0 BC, SLNB was planned and lymphatic mapping depended on each institutional practice. The primary endpoint is FNR of SLNB and secondary endpoints are the identification rate and outcome of ycN0 BC patients at 2 years after surgery. Moreover, in cases of pN0(sn), pN0(i+)(sn) and pN1mi(sn), SLNB followed by lymph node sampling had been allowed instead of axillary lymph node dissection. Based on an estimated FNR of 5%, 224 patients were needed to give 80% power to reject the null hypothesis that the threshold of FNR is 15% with a one-sided type I error rate of 5%. Results: Between February 2018 and May 2021, 185 patients from 19 institutes were registered. After 27 ineligible cases of protocol deviation, non-ycN0 or withdrawal of SLNB were excluded, 158 ycN0 cases underwent SLNB and sentinel lymph nodes were detected in 153 cases. Among them, the median age was 52 years old. Clinical stage was IIA in 40 cases, IIB in 105 and IIIA in 8. Luminal subtype classified by ER, PR and HER2 expression was found in 60 cases, HER2 in 34, Luminal-HER2 in 35 and triple-negative in 24. Finally, 61 cases had positive nodes, which included 7 false-negative cases. FNR was 11.5% (90% confidence interval, 5.5% and 20.5%). The identification rate was 96.8% and the accuracy rate was 95.4%. Before NAC, multimodal imaging was performed in 148 cases (96.7%) and 1 nodal metastasis was detected in 62 cases (40.5%). When multimodal imaging, 1 nodal metastasis, multiple tracers, multiple sentinel lymph nodes were considered for subset analysis, the FNR was 12.1%, 9.1%, 11.1%, and 10.6%, respectively. If isolated tumor cells in lymph nodes had been defined as pathologically negative even after NAC, the FNR was 7.1%. Conclusions: Multimodal imaging could not improve FNR in ycN0 BC. However, SLNB-guided axillary management should be considered when one positive-node is clinically converted to ycN0 after NAC. We will report the outcome of ycN0 BC cases next year. Clinical trial information: UMIN000030558.