We describe a 45-year-old woman who presented with a spontaneous unilateral nipple discharge. With a negative breast examination and screening tests (mammography and ultrasonography) she underwent mammary ductography, which revealed a small 3-4 mm intraluminal filling defect. A core biopsy showed high-grade ductal carcinoma in situ (DCIS). An attempted wide local excision was unsuccessful, and the patient underwent a mastectomy. Pathologic assessment revealed high-grade DCIS and multiple foci of invasive mucinous ductal adenocarcinoma. Rare tumor cells were identified in the subcapsular sinuses in both sentinel lymph nodes. We report this case to point out the importance of the diagnostic examination for patients with a pathologic nipple discharge and review current and possible future diagnostic management.