Penile carcinoma is a relatively frequent health issue in the developing countries such as Africa, Asia and South America, usually affecting men aged between 50 and 70 years. It is a highly treatable disease in its early stages, but has serious physical and psychological consequences. Usually, penile carcinoma is located in the penile glans, in approximately half the cases, with the most frequent histological type being squamous cell carcinoma with its microscopic subtypes. A large number of risk factors have been reported for this disease, having a multifactorial etiology, HPV infection being one of the most important factors involved in its appearance. Out of the HPV DNA positive genital cancers HPV-16 is the most frequently found type in men, followed by HPV-18. The evolution of penile cancer includes two independent carcinogenic pathways, related or unrelated to HPV infection. There is limited data available in literature regarding HPV-related neoplasia, as well as on the efficacy of vaccination in men, with studies still ongoing.