Since tumor growth and metastastatic spread are considered to depend on tumor-stroma interaction, the present study describes the architecture of collagen fibers in 12 cases each of primary melanoma (vertical tumor thickness >1 mm) and common melanocytic nevi in azan-stained sections by using automated image analysis. In each case, at least 100 high-power fields were consecutively sampled from the tumor center, the tumor periphery, and the surrounding normal-appearing reticular dermis. In both diagnostic groups, collagen density (amount of collagen per tissue volume) and mean collagen fiber bundle diameter was significantly lower in the tumor periphery than in the surrounding stroma and again lower in the tumor center than in the tumor periphery. When melanomas and nevi were compared with each other, melanomas had fewer, but thicker, collagen bundles than did nevi, particularly at the tumor periphery. Taking the mean values of each case as classifiers in multivariate logistic regression analysis, 21 of 24 cases were correctly classified (chi-squared test, p < 0.0001), indicating that the parameters of collagen architecture at least in part reflect biological differences between benign and malignant melanocytic skin lesions.