BackgroundFalse-negative rate (FNR) of sentinel lymph node dissection (SLND) has not been eliminated. The study was conducted to optimize the surgical resection of axilla in patients with negative sentinel lymph node (SLN) for the purpose of eradicating false-negative (FN) events of SLND.MethodsA total of 312 clinically node-negative patients without neoadjuvant therapy underwent SLND with indocyanine green (ICG), methylene blue and the combination of ICG and methylene blue. Axillary dissection was performed subsequently regardless of the status of SLN. Lymph nodes were sent for pathological examination separately by serial resection every 0.5cm away from marginally visualized SLNs.ResultsSLND was successfully conducted in 98.1% (306/312) of patients using methylene blue, ICG, and its combination. Further examination revealed 97 true-positive, 189 true-negative, and 13 FN results. The overall FNR was 11.8% (13/110). A horizontal line 1.5cm away from the superior vSLN and a vertical line 1.5cm away from the medial vSLN formed a zone of lower outer quadrant (LOQ) in axilla. Surgical resection of LOQ en bloc' showed a FNR of zero.ConclusionsThe surgical management of axilla may benefit negative SLN patients with potential nodal involvement, reducing the FNR of SLND to zero.Trial registration number and agencyThis study was registered with the Chinese Clinical Trial Registry (ChiCTR1800014247).