Penile cancer is a rare malignancy affecting more than 400 men per year in the UK. Studies on the aetiopathogenesis of this cancer have focused on its association with the human papilloma virus; however, there have also been several studies on the genetic and molecular changes that occur. Human papilloma virus has shown differential levels of prevalence in association with different types of penile cancer. The virus seems to act as a trigger for this disease via its oncogenes. We review this process, and assess the independent genetic events that occur in penile cancer. Knowledge of this cancer is progressing slowly and could be furthered by multicentre cooperation and the formation of national tumour banks, which will aid the development of novel therapeutic agents to reduce the morbidity and mortality of penile cancer.