Comparison of argyrophilic nucleolar organizer region (AgNOR) counts has been found to yield statistically significant differences between benign and malignant conditions albeit with considerable overlap. In this study we compared the size of AgNORs and the nuclear areas, as well as the AgNOR count in 23 benign melanocytic lesions and 9 melanomas. Of these parameters, the ratio AgNOR area/nuclear area was found to be the main discriminating factor between melanoma and all the other benign groups studied, with p values of < 0.01 and no overlap. Next to it was the nuclear area, which in our study gave significant differences between the groups evaluated. The total AgNOR area and the largest AgNOR gave results comparable to the simple AgNOR counting in all groups studied, except in Spitz nevus, in which the AgNOR counts were less significant than the other parameters (p = 0.0420). We conclude that the ratio AgNOR area/nuclear area discriminates benign from malignant melanocytic lesions better than AgNOR counts or other parameters studied.