Xeroderma pigmentosum (XP) is a rare autosomal recessive genetic disorder characterized by defective DNA repair leading to clinical and cellular hypersensitivity to ultraviolet (UV) 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. Oral implications such as severe oral pain and mouth opening limitation were present due to perioral scars. The disorder is associated more commonly in populations where marriage of close blood relatives is common. Treatment of the disorder includes avoidance of UV radiation, topical application of 5-fluorouracil to treat actinic keratoses, and regular evaluation by an ophthalmologist, dermatologist, and neurologist. Genetic counseling is important aspects as an increased incidence of consanguineous marriages have been reported with this disorder. 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.