Objective: To assess the impact of melanoma on the health-related quality of life of patients from the general population up to 10 years after diagnosis and its determinants. Design: A cross-sectional Dutch population-based postal survey among patients with melanoma for the years 1998 to 2008 using the Eindhoven Cancer Registry. Main Outcome Measures: The 36-Item Short-Form Health Survey (SF-36), Impact of Cancer (IOC) questionnaire and specific melanoma-related questions. The SF-36 scores of the cases were compared with normative data. Multiple linear regression models were used to identify associated factors of SF-36 and IOC scores. Results: The response rate was 80%. The mean age of the 562 respondents was 57.3 years; 62% were female, and 76% had a melanoma with a Breslow thickness of less than 2 mm. The SF-36 component scores of patients with melanoma were similar to those of the normative population. In a multiple linear regression model, stage at diagnosis, female sex, age, and comorbidity were significantly associated (P<.05) with the physical and mental component scores. Women were significantly more likely to report higher levels of both positive and negative IOC. Time since diagnosis, tumor stage, and comorbidity were significant predictors of negative IOC scores. Women seemed to adjust their sun behavior more often (54% vs 67%; P<.001) than men and were more worried about the deleterious effects of UV radiation (45% vs 66%; P<.001). Conclusion: The impact of melanoma seems to be specific and more substantial in women, suggesting that they may need additional care to cope with their melanoma optimally.