A case review of 225 patients with abnormal breast nipple secretions (NS) was done to determine diagnostically useful clinical and cytologic features. The cytologic specimens and medical records from all patients and 45 concurrent breast biopsies were reviewed. Nipple discharge was attributed to fibrocystic disease (FCD) in 81 cases, physiologic disturbances in 62, papillomas in 18, ductal carcinoma (CA) in 5, miscellaneous benign disorders in 14, and unknown causes in 45. Although cytologic examination of NS was very specific in identifying malignancy, the sensitivity of cytology was low. Carcinoma was diagnosed or suspected cytologically in only three of the five CA cases, with no false-positive cytopathologic interpretations. Malignant NS were usually unilateral, hemorrhagic, mass-associated, and in older patients. Males with nipple discharge had a significantly higher incidence of breast cancer (two of nine; 22%) than women with abnormal NS (3 of 216; 1.5%). Papilloma NS were generally unilateral and hemorrhagic; FCD and physiologic NS were mostly serous or milky. Benign NS were not cytologically distinguishable. We conclude that cytologic examination of NS is a specific but insensitive method to identify underlying malignancy. Additional clinical features, including patient age, laterality and character of NS, and radiographic findings, were found to be diagnostically useful.