A case of focal epithelial hyperplasia (Heck's disease) of the oral mucosa observed for the first time in Italy is reported. The patient was of Italian extraction. The lesions, represented by soft nodules, were multiple and located on the vestibular and labial mucosa. Biopsy tissues were studied for the presence of human papilloma virus (HPV) by electron microscopy, in situ hybridization and immunoperoxidase staining to HPV group antigens. No viral particles consistent with HPV were found in the epithelial cells. The tissues were positive for HPV antigen by immunoperoxidase staining and hybridized to the HPV 13 probe. In situ hybridization to the HPV 6, HPV 11, HPV 16, HPV 18 and 32 probes was negative. Our study substantiates that focal epithelial hyperplasia, although rare, may be observed in Whites and that HPV 13 in associated with the disease.