Neoplasms of the vulva and vagina together account for less than 5% of all female genital tract cancers, and very few cases have been analyzed using chromosome banding techniques. We report the karyotypic findings in a consecutive series of ten tumors of the vulva and vagina; in addition to five squamous cell carcinomas of the vulva, we present the first cytogenetic analysis of two malignant melanomas and a Paget disease of the vulva, as well as an adenocarcinoma and a squamous cell hyperplasia of the vagina. Whereas no clonal karyotypic changes were found in the squamous cell hyperplasia of the vagina, the remaining nine malignant tumors showed clonal chromosome abnormalities. An inverse correlation was found between the degree of histologic differentiation and karyotypic complexity in the squamous cell carcinomas of the vulva. The malignant melanomas had chromosomal aberrations that have previously been described in malignant melanomas occurring elsewhere, but were less karyotypically complex. Cytogenetically unrelated clones were detected in the Paget disease of the vulva but not in any of the other tumors; this finding is consonant with the interpretation that at least a proportion of Paget disease of the vulva arises multicentrically within the epidermis from pluripotent stem cells.