Using data from a large health plan, we performed a cohort study of thyroid cancer among 204,964 persons (aged 10–89 at baseline in 1964–1973, 54% female) followed for a median of 20 years. There were 196 incident thyroid cancers (73 in men, 123 in women). Risk was independently and positively related to female gender [relative risk (RR) = 1.56, 95% confidence interval (CI) = 1.12–2.19], Asian race (RR = 2.86, 95% CI = 1.76–4.65), completed college or post-graduate education (RR = 1.76, 95% CI = 1.20–2.59), history of goiter (RR = 3.36, 95% CI = 1.82–6.20), radiation of the neck region (RR = 2.33, 95% CI = 1.28–4.23) and family history of thyroid disease (RR = 2.18, 95% CI = 1.17–4.05). An inverse association was found for black race (RR = 0.55, 95% CI = 0.33–0.91). Cigarette smoking, alcohol consumption, personal history of hyperthyroidism, hypothyroidism, overweight or obesity, weight gain since age 20, height, occupational exposures, reproductive factors, oral contraceptives and hormone use did not show statistically significant relations to thyroid cancer. These results provide further evidence for a role of female gender, radiation, goiter, Asian race, high educational attainment and family history of thyroid disease in the etiology of thyroid cancer.