We reviewed 65 intraepithelial lesions of the vulva and distal vagina and compared the presence of koilocytosis, abnormal mitoses, and parabasal or basal nuclear enlargement with DNA microspectrophotometric distribution patterns and the presence of human papillomavirus antigen as determined by immunoperoxidase. Abnormal mitoses and cytologically atypical nuclear enlargement were specific predictors of aneuploidy and were reliable for distinguishing vulvar intraepithelial neoplasia (VIN) from condylomas. Koilocytosis was present in 100% of condylomas and 71% of aneuploid (VIN) lesions, but there were qualitative and quantitative differences in the distribution of koilocytic cells in the two classes of lesions. On the basis of these findings, criteria for distinguishing between VIN and condyloma are proposed.