In order to evaluate the natural history of Vaginal Intraepithelial Neoplasia (VAIN), its epidemiological characteristics and the risk of its evolving into Invasive Carcinoma, we studied direct vaginal biopsies from 376 outpatients, we ascertained the predominant disease site and investigated whether the lesions (uni or multicentric) were only vaginal, were present at both the cervix and the vagina or were an extension of cervical lesions (DES-like areas). Moreover, in cervical and vaginal biopsies from 265 patients, we compared the severity of intraepithelial neoplasia of the vagina and cervix. In our series, vaginal lesions accounted for over half (52.6%) of the alterations attributable to HPV infection, while VAIN accounted for 46.5%; in 84.8% of cases, VAIN was associated with HPV. In 49.8% of cases, biopsies were from the upper third of the vagina and in 74.8% the pathological areas involved both the cervix and the vagina. The DES-like zone accounted for 7.9% of cases, vaginal wall involvement being limited to the upper third. Finally, the comparison of histological findings, in the 265 patients, confirmed that in 69.8% cases vaginal and cervical lesions were of the same grade; in 18.8% vaginal lesions were more severe than cervical lesions. In our study a higher number of vaginal biopsies were taken than in previous years, and it is difficult to establish whether this depends on improved diagnostic methods or on changes in epithemiological factors, such as the reported increase in the incidence of HPV lesions. A systemic search for lesions and a study on their evolution are therefore required to clarify this aspect.