OBJECTIVE Despite its rarity, epidermodysplasia verruciformis was addressed in depth in recent literature. Patients are afflicted by persistent human papillomavirus infections and develop cutaneous malignancies more frequently and younger than in the general population. The disease is therefore considered a model for a viral role in cutaneous oncogenesis, although implication is controversial. We focus on recent findings in genetics, highlight multiple viewpoints regarding the role of epidermodysplasia verruciformis-human papillomavirus in nonmelanoma skin cancer and other diseases, and discuss treatment strategies. RESULTS Susceptibility loci for epidermodysplasia verruciformis were mapped and encoded protein functions are becoming better understood, but a unified genetic theory for epidermodysplasia verruciformis is lacking. Epidermodysplasia verruciformis-human papillomavirus, originally thought present only in epidermodysplasia verruciformis, is now considered ubiquitous, its role still being elucidated. Numerous therapies for epidermodysplasia verruciformis lesions were proposed, although there is no consensual first-line treatment strategy. CONCLUSIONS Discoveries of novel mutations and further study of epidermodysplasia verruciformis-human papillomavirus in lesional and nonlesional skin of epidermodysplasia verruciformis patients and the general population may generate a cohesive theory regarding a viral role in cutaneous oncogenesis. Future understanding of the disease may yield an optimal approach to treating epidermodysplasia verruciformis patients.