〔Abstract〕 Objective To investigate the application value of the ultrasound–guided core needle biopsy (US-CNB) in the differential diagnosis of benign and malignant breast nodules. Methods A total of 102 patients with breast nodules treated in Longyan First Hospital from September 2020 to September 2022 were selected as research objects. US-CNB examination was performed in all patients, followed by surgical treatment, with surgical pathology as the gold standard. The benign and malignant breast nodules were detected by US-CNB and pathological examination. The sensitivity, accuracy, specificity, positive predictive value and negative predictive value of US-CNB in the differential diagnosis of benign and malignant breast nodules were calculated. Kappa analysis was used to examine the consistency of US-CNB and surgical pathology in distinguishing benign and malignant breast nodules. Results Among 102 patients with breast nodules, 50 cases were malignant nodules (49.02 %) and 52 cases were benign nodules (50.98 %). 49 cases of malignant nodules (48.04 %) and 53 cases of benign nodules (51.96 %) were detected by US-CNB. There was no significant difference in the detection rate of benign and malignant nodules between the two groups (P > 0.05). The sensitivity, specificity, accuracy, positive predictive value and negative predictive value of US-CNB test were 98.00 % (49/50), 100.00 % (52/52), 99.02 % (101/102), 100.00 % (49/49) and 98.11 % (52/53) in the differential diagnosis of benign and malignant breast nodules; The results of Kappa analysis showed that US-CNB was consistent with pathological examination in the differential diagnosis of benign and malignant breast nodules (κ = 0.980, P < 0.001). Conclusion US-CNB has the characteristics of high sensitivity and accuracy in the differential diagnosis of benign and malignant breast cancer nodules. It is highly consistent with surgical pathological examination and has less trauma, so it can be used as a scheme for the differential diagnosis of breast nodules.