CONTEXT Radiation exposure is associated with development of thyroid nodules. The long-term risk of thyroid cancer development in irradiated people with thyroid nodules, however, has not been clarified. OBJECTIVE The objective of this study was to assess the long-term risk of cancer development in irradiated individuals with thyroid nodules. DESIGN, SETTING, AND PARTICIPANTS This prospective study comprised 2637 atomic bomb survivors (mean age, 59 yr; 1071 men and 1566 women) who participated in the baseline thyroid study of the Nagasaki Radiation Effects Research Foundation from 1984 through 1987. The participants were divided into three groups at baseline by ultrasound findings: 82 cases of solid thyroid nodules other than cancer, 121 cases of thyroid cysts, and 2434 thyroid nodule-free controls. Both the solid nodule and the cyst groups included postoperative cases. In the solid nodule group, 68 cases had ultrasound-detected solid nodules, including 31 cases diagnosed as benign by cytological or histological examination. They were followed for an average of 13.3 yr. MAIN OUTCOME MEASURE Incident thyroid cancer was measured during an average 13.3-yr follow-up period. RESULTS During the follow-up period, six thyroid cancer cases (7.3%) were found in the solid nodule group, seven cases in the controls (0.3%), and one case (0.8%) in the cyst group. In 31 cases with solid nodules diagnosed as benign, three cases (9.7%) developed thyroid cancer. The hazard ratio (HR) for cancer development was significantly high at 23.6 [95% confidence interval (CI), 7.6-72.8] in the solid nodule group (HR, 40.2; 95% CI, 9.4-173.0 in 31 people with solid nodules diagnosed as benign) but not in the cyst group (HR, 2.7; 95% CI, 0.3-22.2), after controlling for age and sex. Sex, age, TSH level, thyroglobulin level, radiation dose, nodule volume, and increase in nodule volume did not predict cancer development in the solid nodule group. CONCLUSIONS Risk of thyroid cancer development is high in atomic bomb survivors with solid thyroid nodules, suggesting the need for careful observation of irradiated individuals with such nodules.