Polybrominated diphenyl ethers (PBDEs) alter thyroid hormone homeostasis, but their relationship with thyroid cancer is unknown. To investigate whether serum concentrations of PBDE were associated with thyroid cancer, we conducted a nested, case-control study in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, a large multicenter clinical trial in the United States. Cases with thyroid cancer (n = 104) were recruited from 1992 to 2001 and diagnosed through 2009, and controls (n = 208) were individually matched (2:1) to cases by race, sex, birth date (within 1 year), center, and blood collection date (within 15 days). We used gas chromatography isotope dilution high-resolution mass spectrometry to measure 10 tri- to heptabrominated diphenyl eithers in serum samples. Odds ratios and 95% confidence intervals were calculated using conditional logistic regression for lipid-adjusted PBDE levels detected in more than 50% of controls and for the sum of these BDEs (summationPBDEs). We observed no significant differences between cases and controls in lipid-adjusted concentrations of ?PBDEs (for cases, median = 12.8 ng/g lipid (interquartile range, 6.2-42.1); for controls, median = 19.4 ng/g lipid (interquartile range, 7.6u50.2)) or for individual congeners. Increasing quartiles of ?PBDEs and 4 BDE congeners were not associated with risk of thyroid cancer (for the fourth vs. first quartile of summation PBDEs, adjusted odd ratio = 0.62, 95% confidence interval: 0.29, 1.30; P for trend = 0.56). Our study does not support an association between exposure to PBDEs and thyroid cancer.