PURPOSE: The purpose of this study was to retrospectively investigate the reliability of breast ultrasound (US) Breast Imaging Reporting and Data System (BI-RADS) final assessment in mammographically negative patients with pathologic nipple discharge, and to determine the clinical and ultrasonographic variables associated with malignancy in this group of patients. METHODS: A total of 65 patients with 67 mammographically negative breast lesions that were pathologically confirmed through US-guided biopsy were included. RESULTS: Of the 53 BI-RADS category 4 and 5 lesions, eight (15.1%) were malignant (six ductal carcinomas in situ, one invasive ductal carcinoma, and one solid papillary carcinoma). There was no malignancy among the remaining 14 category 3 lesions. Malignant lesions more frequently displayed a round or irregular shape (75.0%, 6/8; p=0.030) and nonparallel orientation (33.3%, 4/12; p=0.029) compared to the benign lesions. The increase in the BI-RADS category corresponded with a rise in the malignancy rate (p=0.004). CONCLUSION: The BI-RADS lexicon and final assessment of breast US reliably detect and characterize malignancy in mammographically negative patients with pathologic nipple discharge.