Xeroderma Pigmentosum is a rare autosomal recessive genetic disorder characterized by defective DNA repair leading to clinical and cellular hypersensitivity to ultraviolet radiation and carcinogenic agents. Important clinical features are: intense cutaneous photosensitivity, xerosis, poikiloderma, actinic keratosis, acute burning under minimal sun exposure, erythemas, hyperpigmented lentiginous macules, and malignant lesions in sun-exposed areas, including basocellular carcinoma, squamous cell carcinoma, and melanoma. There is a great involvement of many parts of the body, especially head and neck. The oral manifestations are mainly related to the occurrence of malignant tumors in the lips, tongue and buccal mucosa. This paper reports a rare case of Xeroderma Pigmentosum in a 41-year-old male presenting mainly dermatological, neurological and ophthalmological involvement. Oral implications such as severe oral pain and mouth opening limitation were present due to perioral scars. In addition, this paper discuss some important aspects concerning the role of the dental professional management of this entity, since XP patients require constant dental care and follow-up in order to control the occurrence of new lesions on the lips or inside oral cavity.