Squamous papillae of the vulvar vestibule and introitus are quite a common clinical finding, however their origin is uncertain. They were formerly described as a normal variant of the mucosal epithelium, but recently they have been attributed to human papillomavirus (HPV) infection. Eight women with clinical findings compatible with a diagnosis of vulvar squamous papillomatosis were studied. All were free of other clinically evident HPV-related diseases. Vulvar scrapes and biopsy specimens were collected and used for DNA extraction and microscopic examination. DNA extracted from vulvar scrapings and from paraffin-embedded tissue was subjected to polymerase chain reaction (PCR). The reactions were performed with two sets of primers designed for the amplification of numerous HPV genotypes including those most commonly encountered in the genital area. Histological examination failed to reveal clear-cut signs of HPV infection in any subject. The PCR on the DNA extracted from vulvar scrapings revealed HPV infection in two cases. PCR performed on the DNA extracted from the paraffin-embedded tissue failed to detect HPV-DNA in any case. A 6-month follow-up showed no changes in the lesions. These results along with literature data, which is clearly inconsistent, indicated that the presence of HPV is coincident to, rather than causal of, vulvar squamous papillomatosis lesions. Patients with symmetrically distributed, long-standing vulvar papillae should, therefore, be carefully evaluated before starting therapy.