Objective: To evaluate galactography and cytology in women with nipple discharge without clinical or mammographic evidence of cancer. Methods: During a 12.5-year period, 384 women (15-85 years, mean age 47.5 +/- 14 years) were referred for galactography and smear cytology for recent onset of spontaneous, non-milky nipple discharge. Patients with clinical or mammographic evidence of tumor underwent excisional biopsy directly. Among 314 galactograms, 189 [60.2%; 95% confidence interval (CI) 54.5%, 65.6%] biopsies were recommended. A further 11 patients were scheduled for biopsy because of mammography or cytology. Results: Sixteen of 182 biopsied patients had malignancies (8.8%; CI 5.3%, 14.1%). Combined rate of papillomas, papillomatous proliferation, and malignant tumors was 59.9% (109 of 182; CI 52.4%, 67.0%). Biopsy was malignant in three of 56 women (5%) with nonhemorrhagic discharge and in 13 of 97(13%) with hemorrhagic discharge (P = .26). Exfoliative cytology revealed 11 false-negatives, four false-positives, five true-positives, and 153 true-negatives (sensitivity 31.2%, CI 11%, 58%; specificity 97.4%, CI 93%, 99%). In ten of 158 patients (6.3%) with suspicious galactography, cancer was found by biopsy. Sensitivity of galactography for malignancy was 83% (CI 51.6%, 97.9%) and specificity was 41% (CI 35.2%, 46.5%). Galactographic sensitivity for any (benign or malignant) neoplasm was 94% (93 of 99; CI 87%, 98%) and specificity was 55% (119 of 215; CI 48%, 62%). Half of the cancers were detected exclusively by galactography. Conclusion: Cytology is helpful when positive and galactography localizes the source of discharge. Biopsy is indicated when palpation, mammography, cytology, or galactography is suspicious. (C) 2001 by The American College of Obstetricians and Gynecologists.