Sleep disturbance has been found to be associated with numerous adverse health outcomes, including cancers. However, no epidemiologic study has examined the relation between sleep disturbance and thyroid cancer risk. A total of 142,933 postmenopausal women who were 50-79 years of age and enrolled in the Women's Health Initiative between September 1, 1993, and December 31, 1998, were followed up for a mean of 11 years. Cox proportional-hazard regression models were used to estimate hazard ratios and 95% confidence intervals for sleep disturbance (insomnia and sleep duration) and risk of thyroid cancer. Insomnia score was measured using a validated 5-item Women's Health Initiative Insomnia Rating Scale. Overall, a total of 295 thyroid cancer cases were identified. After adjustment for potential confounders, women with greater insomnia scores had a significantly higher risk of thyroid cancer than did women with low scores (hazard ratio = 1.44, 95% confidence interval: 1.01, 2.05). The significant association between insomnia score and thyroid cancer was confined to nonobese women (hazard ratio = 1.71, 95% confidence interval: 1.12, 2.62) and was not seen in obese women (hazard ratio = 0.94 95% confidence interval: 0.48, 1.84) (P for interaction = 0.07). In conclusion, postmenopausal women with greater insomnia scores, especially nonobese women, had a significantly increased risk of thyroid cancer. More studies are needed to confirm these findings.