Background: In order to elucidate criteria for distinguishing benign from malignant lesions, this study correlated the ductoscopy-based macroscopic description of intraductal lesions with histopathologic results. Materials and Methods: Aiming to use diagnostic criteria consistent with previous publications, we analyzed the literature and established a uniform set of diagnostic descriptors. Based on these criteria, we subsequently analyzed and catalogued video and photographic material from 68 patients with nipple discharge, who had undergone ductoscopy followed by open surgery. For all breast lesions, the factors lesion type, number of lesions, lesion color, surface characteristics, and presence of blood or atypical vessels were reported. Based on the frequency distribution and the odds ratio, we were able to evaluate the differential diagnostic value of ductoscopic criteria in comparison with the respective histopathologic results. Results: Among the ductoscopic criteria, a fissured surface, hemorrhage or atypical vessels, and a polypoid appearance were important predictors for malignant lesions. In contrast, a smooth surface, the absence of hemorrhage and atypical vessels and a level appearance of the lesions predicted benign lesions. Conclusions: For predicting the benign versus malignant character of ductoscopic lesions, the following criteria should be used: presence or absence of blood and atypical vessels, surface type, and level versus polypoid appearance.