Melanoma is nowadays a major public health problem because of its increasing incidence. Targeted screening for patients at a high risk for melanoma is being promoted. The aim of our study was to assess the effectiveness of a targeted screening on the basis of the self-selection of high-risk individuals with the Self-Assessment of Melanoma Risk Score (SAMScore). Our main objective was to prove that this score allows the selection of a group of patients who are at a higher risk and in whom more melanomas may be detected. This prospective study was carried out in France in 2009. Consecutive patients, while visiting their doctor's office, filled out a melanoma risk factor questionnaire. Patients were assessed as being at high risk or not according to the SAMScore, and patients at a high risk were examined both by their general practitioner and by a dermatologist. The efficiency of the selection tool corresponded to the ratio of the prevalence of melanoma in a population selected with the SAMScore to the prevalence in the general population. A logistic model with a random effect was used. A total of 7977 patients filled out the questionnaire. Among the 2404 patients at high risk, histologically proven melanoma was screened in 10 cases: two in-situ and eight invasive melanomas. The SAMScore efficiency assessed was equal to 11.54 (P=0.0016). In conclusion, in this strategy, to detect a new case of melanoma, it is necessary to screen 11 times fewer patients than with a nontargeted screening. This is the first study to confirm the efficiency of a targeted screening on the basis of self-selection of high-risk individuals.