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Background Objectives Materials and Methods Results Discussion and Conclusion The most prevalent sexually transmitted disease in the world has the human papillomavirus (HPV) as its etiological agent.To evaluate the prevalence of previous and actual HPV infection and the clinical manifestations in unselected males.A total of 718 males participating to a surveillance program were asked to complete a study visit at our unit, including semen collection, balanopreputial sulcus swab, and blood collection for total anti‐HPV immunoglobulin G (IgG). When HPV‐DNA was detected, we performed HPV fluorescence in situ hybridization, oral and anal swab, and penoscopy. Because previous studies demonstrated a very high risk for HPV infection in subjects with history of HPV‐induced lesions, with a partner with diagnosed HPV infection or reporting couple infertility or sexual promiscuity and an increase of the risk in males having sex with males, in subjects with unprotected sexual intercourses or in heavy smokers, patients were therefore stratified according to the presence of these known risk factors (RFs).Actual HPV infection was detected in 401/718 subjects (55.85%). Oral HPV‐DNA was reported in 80 subjects and anal HPV infection in 52 subjects. Anti‐HPV IgG antibodies have been detected in 288 subjects. The overall prevalence of HPV exposition, considering actual and/or previous infection was 77.99%. Among infected men, high‐risk HPV genotypes were detected in 66.08%.A total of 514 subjects were considered as the RF population, while 150 were classified in the non‐RF population. There was a significantly higher prevalence of condylomatosis (odds ratio [OR] 4.07) and of seminal infection (OR 6.22) in the RF group.These data represent an alert for the healthcare system to perform informative and screening campaigns for HPV infection in males and to promote HPV vaccination both in young people and for adult males with RF for HPV infections. [ABSTRACT FROM AUTHOR]