Objective To identify changes in incidence of cutaneous melanoma over time in the fastest-growing segment of the US population, middle-aged adults. Patients and Methods Using the Rochester Epidemiology Project resource, we identified patients aged 40 to 60 years who had a first lifetime diagnosis of melanoma between January 1, 1970, and December 31, 2009, in Olmsted County, Minnesota. Incidence of melanoma and overall and disease-specific survival rates were compared by age, sex, year of diagnosis, and stage of disease. Results From 1970 through 2009, age- and sex-adjusted incidence increased significantly over time (P<.001) from 7.9 to 60.0 per 100,000 person-years, with a 24-fold increase in women and a 4.5-fold increase in men. Although not significant (P=.06), incidence of melanoma increased with age. Overall and disease-specific survival improved over time, with hazard ratios of 0.94 (P<.001) and 0.93 (P<.001) for each 1-year increase in year of diagnosis, respectively. Each 1-year increase in age at diagnosis was associated with increased risk of death from any cause (hazard ratio, 1.07; P=.01) but was not significantly associated with disease-specific death. Sex was not significantly associated with death from any cause or death from disease. No patient with malignant melanoma in situ died from disease. Patients with stage II, III, and IV disease were over 14 times more likely to die from disease compared with patients with stage 0 or I disease (P<.001). Conclusion The incidence of cutaneous melanoma among middle-aged adults increased over the past 4 decades, especially in middle-aged women, while mortality decreased.