BACKGROUND: Human Papillomavirus (HPV) is a common sexually transmitted infection (STI), representing the main cause of genital warts and cervical cancer. This cross-sectional study evaluated knowledge and attitudes about HPV infection, related diseases, and prevention and propensity towards HPV vaccine among undergraduate students. METHODS: An online and written survey about HPV and its prevention, targeted to young adults of both genders, was addressed to students attending health sciences and other schools at Universities of Genoa and Bari. RESULTS: The overall median knowledge and attitude scores were 56.3% (25-75 = 40-68.8%) and four out of five (25-75 = 4-5), respectively. In the multivariate analysis, attending a health sciences university, using social networks ≤2 h a day, a history of STI, having heard about HPV and HPV vaccine previously resulted as predictors of higher knowledge scores. Having heard about HPV previously also predicted a high attitude score, together with a perceived economic status as good. Having Italian and healthcare worker parents, being employed, and following a specific diet, instead, predicted lower attitude score. CONCLUSIONS: Poor knowledge and good attitudes were found among undergraduates about HPV. In order to increase HPV vaccine compliance and the counselling skills of future healthcare workers, the improvement of training on HPV is needed.