Epidermodysplasia verruciformis has been addressed in depth in the recent literature despite its rarity. The disease is characterized by a persistence in human papillomavirus infections and development of cutaneous malignancies, usually happening more frequently and at a younger age than in the general population. Because of the role of immunodeficiency to viral antigens eventually leading to cancer, EV has become a model for understanding a viral role in cutaneous oncogenesis. Susceptibility loci for EV have been mapped and encoded protein functions are becoming better understood. Discoveries of novel mutations and further study of EV-associated HPV serotypes in lesional and nonlesional skin of affected patients and the general population may help generate a cohesive theory regarding the true role of a defective immune barrier in oncogenesis.