Fiberoptic ductoscopy system (FDS) offers a safe alternative to ductography in diagnosing intraductal lesions and serves as a guide for subsequent surgery in women with nipple discharge. In this article, we reported the outcomes of FDS combined with cytology testing for diagnosis of spontaneous nipple discharge. From 1997 to 2005, 1,048 women (1,093 breasts total) in the outpatient department underwent successful diagnostic FDS. Discharge was unilateral (86.8%), single ductal (93.4%), and serous (57.9%) or bloody (36.0%). Among 437 (40.0%) of the FDS-positive breasts, we revealed 49 (11.2%) breast carcinomas, 228 (52.2%) central papillomas, and 5 (1.1%) cases of atypical ductal hyperplasia. Ten patients with positive cytology testing received microdochectomy in spite of having a negative FDS, which revealed two additional ductal carcinomas in situ (DCIS), and four papillomas. About 489 breasts were negative for both FDS and cytology testing and were subjected to follow up. About 77 (15.7%) of the breasts underwent tissue diagnosis within a median follow-up time span of 19 months, and one DCIS was detected. The sensitivity of FDS for detection of malignant lesions was 94.2% and increased to 98.1% when combined with cytology testing. Nevertheless, it was less sensitive (p<0.01) if we used cytology testing only (58.3%), mammography (48.6%), high-frequency sonography (36.4%), or combination of mammography and sonography (56.8%) to detect these malignant lesions. These data confirmed the value of FDS combined with cytology testing as a diagnostic procedure in women with nipple discharge.