The purpose of this study was to evaluate the accuracy of indocyanine green (ICG) fluorescence imaging versus the gold standard of 99mTc-nanocoilloid for mapping sentinel lymph nodes (SLNs). Radioisotope technetium (99mTc) guided surgery using sentinel lymph node biopsy (SLNB), sometimes in combination with blue dye, is the current gold standard for axillary staging in patients with breast cancer. ICG fluorescence imaging is an alternative that shows promise. Researchers enrolled 102 consecutive patients with invasive early-stage breast cancer who were clinically node-negative for this noninferiority trial. Patients were scheduled to have SLNB in conjunction with breast-conserving surgery between August 2020 and June 2021. Patients were given injections of 99mTc-nanocolloid the day or morning before surgery. After performing SLNB with ICG-fluorescent imaging on each patient, they examined the ex vivo uptake of 99mTc in the lymph nodes and the axilla using the gamma-probe. The percentage of patients in whom either tracer detected at least 1 (S)LN was used to calculate the detection rate. As many as 103 SLNBs were studied during this study. ICG-fluorescence was detected at a rate of 96.1% [(95% CI)=90.4%-98.9%] but 99mTc-nanocoilloid was only detected at a rate of 86.4% [95% CI=78.3%-92.4%)]. In a comparison of ICG with 99mTc-nanocoilloid, the detection rate for diseased lymph nodes was 86.7% (95% CI=59.5%-98.3%). The removal of a median of 2 lymph nodes. There was no noticeable delay in detection using ICG-fluorescent imaging. Fortunately, nobody got sick. The detection rate for benign (S)LNs was greater with ICG-fluorescence than with  99mTc-nanocoilloid, and was similar for pathogenic (S)LNs. In patients with early-stage breast cancer, ICG-fluorescence may be utilized as a safe and effective alternative to 99mTc-nanocoilloid for SLNB.