Objective: To examine the prospective association of early age-related macular degeneration (AMD) with cancer mortality. Methods: A population-based cohort study of 10 029 persons aged 49 to 73 years free of cancer. The AMD signs were evaluated from retinal photographs taken in 1993 through 1995. Cancer mortality was determined from death records. Results: There were 464 cases of early AMD. Over 10 years, there were 234 cancer deaths (71 lung cancer deaths). After controlling for age, sex, race, field center, education, smoking status, pack-years of smoking, body mass index (calculated as weight in kilograms divided by height in meters squared), and diabetes mellitus, early AMD was associated with cancer mortality (rate ratio [RR], 1.68; 95% confidence interval [CI], 1.03-2.73). This association was overall stronger in African American individuals (RR, 3.93; 95% CI, 1.67-9.22) than white individuals (RR, 1.28; 95% CI, 0.71-2.32) and for lung cancer deaths (RR, 2.14; 95% CI, 0.97-4.72) than non-lung cancer deaths (RR, 1.50; 95% CI, 0.81-2.78). In African American individuals, early AMD was associated with a 5-fold higher risk of lung cancer deaths (RR, 5.28; 95% CI, 1.52-18.40). Conclusions: Middle-aged African American individuals with early AMD may be at increased risk of dying of cancer, particularly lung cancer. This association was not present in white individuals and needs confirmation in other studies.