Although thyroid cancer is suspected to have a nutritional etiology, prospective studies examining the relationship between diet and thyroid cancer are lacking. During 1996-1997, NIH-AARP Diet and Health Study participants, ages 51-72 years, completed a 37-item food frequency questionnaire about diet at ages 12-13 years (adolescence) and 10 years before baseline (mid-life). Over a median 10 years of follow-up, 325 individuals (143 men and 182 women) were diagnosed with thyroid cancer. Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for intakes of foods and food groups comparing the highest to the lowest quartiles. Adolescent intakes of chicken/turkey (HR = 1.59, 95% CI: 0.97-2.60; ptrend  < 0.01) and sweet baked goods (HR = 1.59, 95% CI: 1.09-2.34; ptrend  = 0.04) were positively associated with thyroid cancer risk, while intake of butter/margarine was inversely associated with risk (HR = 0.64, 95% CI: 0.44-0.91; ptrend  < 0.02). Similar to adolescent diet, mid-life intake of sweet baked goods was nonsignificantly associated with an increased risk of thyroid cancer (HR = 1.39, 95% CI: 0.96-2.00; ptrend  = 0.11), but intake of butter/margarine was inversely associated with risk (HR = 0.66, 95% CI: 0.46-0.95; ptrend  = 0.03). Among men, higher adolescent consumption of canned tuna was positively associated with risk of thyroid cancer (HR = 1.69, 95% CI: 1.01-2.83; ptrend  = 0.03), and greater mid-life intake of broccoli was associated with a twofold increased risk (HR = 2.13, 95% CI: 1.13-3.99; ptrend  < 0.01). This large prospective study suggests that several components of the adolescent and mid-life diet, including iodine-rich foods and goitrogens, may influence thyroid cancer risk.