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Background: The necessity of performing a sentinel lymph node biopsy in patients with clinically and radiologically node-negative breast cancer after neoadjuvant chemotherapy has been questioned. The aim of this study was to determine the rate of nodal positivity in these patients and to identify clinicopathological features associated with lymph node metastasis after neoadjuvant chemotherapy (ypN+). Methods: A retrospective multicentre study was performed. Patients with cT1–3 cN0 breast cancer who underwent sentinel lymph node biopsy after neoadjuvant chemotherapy between 2016 and 2021 were included. Negative nodal status was defined as the absence of palpable lymph nodes, and the absence of suspicious nodes on axillary ultrasonography, or the absence of tumour cells on axillary nodal fine needle aspiration or core biopsy. Results: A total of 371 patients were analysed. Overall, 47 patients (12.7%) had a positive sentinel lymph node biopsy. Nodal positivity was identified in 22 patients (29.0%) with hormone receptor+/human epidermal growth factor receptor 2− tumours, 12 patients (13.8%) with hormone receptor+/human epidermal growth factor receptor 2+ tumours, 3 patients (5.6%) with hormone receptor−/human epidermal growth factor receptor 2+ tumours, and 10 patients (6.5%) with triple-negative breast cancer. Multivariable logistic regression analysis showed that multicentric disease was associated with a higher likelihood of ypN+ (OR 2.66, 95% c.i. 1.18 to 6.01; P = 0.018), whilst a radiological complete response in the breast was associated with a reduced likelihood of ypN+ (OR 0.10, 95% c.i. 0.02 to 0.42; P = 0.002), regardless of molecular subtype. Only 3% of patients who had a radiological complete response in the breast were ypN+. The majority of patients (85%) with a positive sentinel node proceeded to axillary lymph node dissection and 93% had N1 disease. Conclusion: The rate of sentinel lymph node positivity in patients who achieve a radiological complete response in the breast is exceptionally low for all molecular subtypes. A multicentre study of 371 patients with clinically and radiologically node-negative breast cancer treated with neoadjuvant chemotherapy followed by a sentinel lymph node biopsy was performed to evaluate the rate of nodal positivity. Overall, 12.7% had a positive sentinel lymph node biopsy. The rate of sentinel lymph node positivity in patients who achieved a radiological complete response in the breast was exceptionally low (less than 3%) for all molecular subtypes. [ABSTRACT FROM AUTHOR]