Background: Current international guidelines recommend omitting axillary lymph node dissection (ALND) based on sentinel lymph node biopsy (SLNB) in early-stage breast cancer patients. However, the evolving landscape of axillary management highlights the need to balance diagnostic accuracy with minimizing invasiveness. The possibility of omitting SLNB itself should also be considered. Methods: In this study, we have evaluated the feasibility of omitting SLNB in a total of 1044 clinically node-negative (cN (-)) breast cancer patients whose SLN status was determined by histopathology and one-step nucleic acid amplification (OSNA) after SLNB. We also analyzed SLN-positive cases to explore the association between non-SLN (NSLN) metastatic status and various biomarkers. We predicted the metastatic status of NSLNs based on patient data using a nomogram and further assessed the prevalence of macro- and micro-metastatic SLN, along with the NSLN status in SLNB cases. Results: Of the 644 cN (-) cases, approximately 70% of SLN-positive cases were NSLN negative, suggesting that ALND could be omitted. SLN (+) was detected approximately 7% more often by OSNA than by histopathology, suggesting that OSNA detection may be an overdiagnosis. Although NSLN-positive cases represented only 5.9% of the 581 cN (-) cases and, therefore, ALND could be omitted, it may be difficult to omit the SLNB itself as the SLN macro-metastasis was 12.5%. Biomarker analysis showed a significant correlation between total tumor load and metastatic SLN copy number with NSLN metastatic status. Based on these tumor characteristics, the nomogram predicted NSLN-positive rates very well. Conclusions: Thus, omitting SLNB itself carries the risk of missing high-frequency macro-metastatic SLN-positive cases and losing important SLN-related information that can predict NSLN metastases. Therefore, SLNB, which provides not only SLN status but also NSLN metastases, is necessary for reassurance in omitting ALND.