BACKGROUND: In early breast cancer, a non-invasive method with higher sensitivity and negative predictive value (NPV) is needed to identify and recognize more indolent axillary lymph nodes (ALNs). This study aimed to assess whether a novel high-resolution dedicated ALN positron emission tomography (LymphPET) system could improve sensitivity in detecting early breast cancer (clinical N0-N1 stage). METHODS: A total of 103 patients with clinical stage T1-2N0-1M0 breast cancer were evaluated by F-fluorodeoxyglucose (F-FDG) LymphPET. The maximum single-voxel PET uptake value of ALNs (maxLUV) and the tumor-to-background ratio (TBR) for fat (TBR1) and muscle (TBR2) tissue were calculated. Then, 78 patients with cN0 stage breast cancer received sentinel lymph node biopsy alone or combined with axillary lymph node dissection (ALND), and 25 patients with cN1 stage breast cancer underwent fine-needle aspiration. RESULTS: A total of 99 invasive breast carcinoma cases were included in this study. The diagnostic sensitivity of LymphPET was 88%, specificity was 79%, false-negative rate was 12%, the false-positive rate was 21%, positive predictive value was 75%, NPV was 90%, and accuracy was 83%. The maxLUV was superior to TBR1 and TBR2 in detecting ALNs, with 0.27 being the most optimal cutoff value. CONCLUSIONS: The F-FDG LymphPET system can be used to identify and recognize more indolent ALNs of breast cancer due to greater sensitivity and a much higher NPV.