The general objective of this article is to review the current literature regarding the epidemiology, biological behavior and risk factors for penile cancer development, such as HPV infection. Phimosis and chronic irritation related to poor hygiene are commonly associated with penile cancer, whereas neonatal circumcision reduces the relative risk for the disease. There is strong evidence that HPV types 16 and 18 are associated with penile carcinoma in as many as 50% of cases. Patients with penile lesions should undergo physical examination, which is often sufficient to diagnose and to define tumor stagging, as well as contributes to decision-making regarding therapeutical approaches and case management.