AbstractBackground Warts often present a difficult treatment problem for clinicians because of the lack of specific antipapillomavirus agents. Plantar warts, in particular, represent a therapeutic challenge. Methods Twenty-five patients with plantar warts were treated with Nd:YAG hyperthermia and another 25 were treated with cryotherapy. Biopsies were taken before and after treatment in both groups and were examined for the presence of human papillomavirus deoxyribonucleic acid (HPV DNA) using in situ hybridization (ISH). Results HPV DNA was detected in 100% of untreated warts and in 96% of cryotreated warts, but was not detected in any of the hyperthermia-treated warts. Conclusions HPV is more vulnerable to hyperthermia than to cryotherapy.