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Some clinical, pathological and genetic features have been associated to familial melanoma, particularly multiple melanoma and earlier age at diagnosis. To compare the clinical, epidemiological and pathological differences between familial and sporadic melanoma patients in Valencia, Spain, a series of 959 patients with cutaneous melanoma were selected at a single institution. For this study the following variables were selected: age, sex, melanoma site and presence of solar lentigines on the melanoma surrounding skin, histological subtype, tumor thickness, stage, family and personal history of cutaneous melanoma and of other neoplasias, personal history of non-melanoma skin cancer, past personal history of severe sunburns, cutaneous phenotype (phototype, hair and eyes colors number of common nevus, number of atypical nevi, presence of solar lentigines). Forty-one (4.28%) familial and 918 sporadic melanoma were identified. Among the multiple variables studied, a younger age at diagnosis (median age of 42 vs 53 years), higher frequency of the presence of at least one clinically atypical nevus (36.1% vs 17.7%), multiple melanomas (12.2% vs 3.4%) and red/blonde hair (33.3% vs 18.9%), and a lower rate of cases with solar lentigines in melanoma site (33.3% vs 56.3%) were found for familial cases. Except for hair color and age, the other variables remained statistically significant after the multivariate study. Interestingly, no acral melanomas were found among the familial cases. In summary, phenotypic risk factors for familial melanoma are a tendency to develop multiple melanomas, to have clinically atypical nevi and to present less actinic damage at the melanoma site. All these results enhance the relevancy of genetic susceptibility associated to the ability to produce atypical nevi and partly to a higher sensitivity to the sun. [ABSTRACT FROM AUTHOR]