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• In 3414 women with vulvar lichen sclerosus we found 299 subsequent cancers. • We found an increased risk of vulvar, vaginal and oropharyngeal cancer. • Patients with vulvar lichen sclerosus need regular gynecological follow-up. • Checks of oropharyngeal cavity are also recommended. Vulvar lichen sclerosus is a chronic inflammatory disease involving vulvar skin. The risk of developing invasive vulvar cancer for women with LS is reported in the literature, but the risk of extra-vulvar tumors has been under-investigated. This multicentric study aims to estimate the risk of developing cancers in a cohort of women with a diagnosis of vulvar lichen sclerosus. A cohort of women diagnosed with and treated for vulvar lichen sclerosus in three Italian gynecological and dermatological clinics (Turin, Florence, and Ferrara) was retrospectively reviewed. Patient data were linked to cancer registries of the respective regions. The risk of subsequent cancer was estimated by dividing the number of observed and expected cases by the standardized incidence ratio. Among 3414 women with a diagnosis of vulvar lichen sclerosus corresponding to 38,210 person-years of follow-up (mean 11.2 years) we identified 229 cancers (excluding skin cancers and tumors present at the time of diagnosis). We found an increased risk of vulvar cancer (standardized incidence ratio = 17.4; 95 % CL 13.4–22.7), vaginal cancer (standardized incidence ratio = 2.7; 95 % CL 0.32–9.771), and oropharyngeal cancer (standardized incidence ratio = 2.5; 95 % CL 1.1–5.0), and a reduced risk of other gynecological tumors (cervical, endometrial, ovarian) and breast cancer. Patients with vulvar lichen sclerosus should undergo annual gynecological check-up with careful evaluation of the vulva and vagina. The increased risk of oropharyngeal cancer also suggests the need to investigate oropharyngeal cavity symptoms and lesions in patients with vulvar lichen sclerosus. [ABSTRACT FROM AUTHOR]