Although spontaneous nipple discharge without mass is a common complaint, only about 5-15% of patients with nipple discharge have cancer. The standard preoperative evaluations, including mammography, physical examination, ultrasonography and squeezing cytology, do not provide enough definite data to make a decision for surgery. We have investigated whether preoperative intraductal aspiration cytology and galactography supply sufficient information about the location and nature of the lesion, and have carried out a one-step operative procedure by adding frozen section diagnosis during surgery. A retrospective review of Kaohsiung Medical University Hospital patients presenting symptoms of nonpalpable mass was conducted from January 1989 to June 2000. The medical charts, pathology and cytology reports, and imaging studies were reviewed. Of 487 patients with spontaneous nipple discharge, 190 with pathologic discharge had complete preoperative galactography and intraductal aspiration cytology, and 176 received surgery. Fourteen cases with negative cytology and normal galactography, who had not had an operation, did not develop cancer during an average 7 years follow-up. The diagnostic accuracy rates of 35 cancer patients using galactography and cytology were 91.4% and 88.6%, respectively, and 97.1% in combination, which is better than those of 141 patients with benign lesions (77.3% and 84.4%, and 90.0% in combination, P<0.05). The results show a 91.5% preoperative diagnostic accuracy rate in all patients with nipple discharge, and can be used to discuss the diagnosis with the patient during the preoperative period. All 35 cases with cancer received the one-step procedure under general anesthesia. Sixteen patients received mastectomies, and the other 19 cases had ductolobular resections, depending on their preoperative evaluations and frozen section in pathology. There were no false positives or false negatives in frozen section when comparing permanent histology and residual cancer in mastectomy specimens. There were no symptoms of recurrence in any of the patients who had undergone the two different procedures during 7 years of follow-up. In patients with spontaneous nipple discharge without palpable mass, the preoperative intraductal cytology and galactography were reliable methods to evaluate intraductal lesions. The one-step procedure will be selected for those patients if the frozen section is added. The ductolobular resection with an adequate surgical margin should be the first choice for those nonpalpable breast cancers with nipple discharge. Due to the limited number of breast cancer cases studied, more cases and a long follow-up period are necessary in future.