In a plantar cyst composed of the wall of the squamous cell layer and the horny inner substance in the lower dermis, we found characteristic pathological changes, such as cytoplasmic eosinophilic inclusions and vacuolated structure, and, immunohistochemically, the papillomavirus capsid antigen. The human papillomavirus (HPV) DNA cloned from the cyst showed no homology with other known prototypes of HPV (HPV 1 through HPV 59) by Southern blot analysis under stringent conditions and was named as HPV 60. HPV 60 DNA was found in three other cases of plantar cyst with the identical pathological changes, but not in a plantar cyst without such changes. The results suggest that HPV 60 has unique biological properties to induce a plantar cyst as a distinct type of cutaneous HPV.