Abstract Xeroderma Pigmentosum (XP) is a rare autossomic recessive hereditary disorder in which normal ability to repair DNA damage caused by ultraviolet light (UV) is deficient due to the presence of mutations in nucleotide excision repair pathway genes (XPA, ERCC3, XPC, ERCC2, DDB, ERCC4 and ERCC5) or in POLH gene, responsible for the replication of damaged DNA on the leading strand. These different genetic alteration result in distict phenotypes classifified into eight genetic complementation sub groups, XP-A to XP-G and a variant group XP-V. Clinical characteristics of the syndrome include skin poikiloderma and eye hypersensibility to UV radiation. Carriers have an increased risk of early onset multiple cutaneous, mucocutaneous and ophthalmologic malignancies when compared with normal population. Occasionally neurological impairment is observed in certain variations of the syndrome. Given the paucity of specific literature data about the incidence and clinical profile of the disease in Brazilian population, this study was conducted to describe clinical diversity and tumor spectrum of XP syndrome in Brazilian population. Twenty-nine XP patients from 19 non-related families from Hospital A.C. Camargo (São Paulo, Brazil), Hospital Universitário Alcides Carneiro (Campina Grande, Paraíba) and Hospital de Clínicas de Porto Alegre (Rio Grande do Sul, Brazil). Data collection was performed after genetic counseling and signed informed consent. Clinical characteristics were obtained through medical ascertainment. The median age was 24 (4 to 61 years) in a predominant female population (19/29). Basal cell carcinomas (BCC) were the most frequent neoplasm, present in 86,20% (25/29) of all patients, with the occurrence of up to 60 BCCs in a same patient. Squamous cell carcinomas and melanoma were present in 66,7% and 37,5% respectively. Six patients developed the first malignant tumor before the age of six and four patients developed the first tumor in early adulthood. One male patient developed a diffuse gastric cancer at 50 years old. Visual impairment occurred in 45,83% of the patient. Despite the unknown frequency of affected patients, the Brazilian population of XP cases seems to be underestimated. Genetic counseling is fundamental to provide information to carriers and family members and enable preventive measurements. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1837. doi:10.1158/1538-7445.AM2011-1837