The aim of this study was to evaluate the clinical impact of the preoperative ¹⁸F-FDG PET/CT in the initial workup of breast cancer with clinically negative axillary nodes. Whether the status of the clinical axillary nodal involvement can be considered a parameter for making a decision to omit the preoperative ¹⁸F-FDG PET/CT in the situation reported herein was also determined. A total of 178 patients who had newly diagnosed breast cancer and for whom the conventional diagnostic modalities showed no sign of axillary node metastasis were retrospectively enrolled in this study. All the patients underwent preoperative ¹⁸F-FDG PET/CT. The images and histologic results that were obtained were analyzed. ¹⁸F-FDG PET/CT detected primary lesions in 156 of the 178 patients, with an overall sensitivity of 87.6 %, and false negative results were obtained for 22 patients (12.4 %). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of ¹⁸F-FDG PET/CT in the detection of axillary nodes were 20.8, 86.9, 37.0, 74.8, and 69.1 %, respectively. Extra-axillary node metastasis was identified in two patients (1.1 %) who had internal mammary nodes. There was no distant metastasis, but coexisting primary tumor was detected in five patients (2.8 %). In total, the therapeutic plan was changed based on ¹⁸F-FDG PET/CT in seven (3.9 %) of the 178 patients, but considering only the cases confined to breast cancer, the change occurred in only two patients (1.1 %). ¹⁸F-FDG PET/CT almost did not affect the initial staging and treatment plan in breast cancer with clinically negative axillary node. If the axillary node is clinically negative in the preoperative workup of breast cancer, then ¹⁸F-FDG PET/CT can be omitted.