HPV-40 is a rare HPV type that has been detected only in genital mucosal tissues. This HPV type is very closely related to HPV-7, which has a predominantly cutaneous tissue tropism. We have shown, previously, that an isolate of HPV-40 (described here as HPV-40Hershey or HPV-40H) productively infected genital tissues. In this study, HPV-40H was tested for productive infection of cutaneous tissue. Fetal hand skin fragments were incubated with infectious HPV-40H and implanted subrenally into athymic mice. After 120 days, xenografts showed morphological changes consistent with HPV-40H infection and were HPV-40 DNA in situ positive and capsid antigen positive. The results demonstrated that hand skin can support HPV-40H infection thereby indicating that this viral type has the capacity to infect both genital mucosal and cutaneous tissues. © 2003 Elsevier Science B.V. All rights reserved.