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Polychlorinated biphenyls (PCBs) and organochlorine pesticides have been associated with altered thyroid hormone levels in humans, but their relationship with thyroid cancer is unknown.We conducted a nested case-control study of thyroid cancer in the Norwegian Janus Serum Bank cohort using pre-diagnostic blood samples from 1972 to 1985. Incident thyroid cancer (n = 108) was ascertained through 2008. Controls were matched 2:1 by age, date of blood draw, gender, and county. We used gas chromatography/mass spectrometry to quantify 36 PCB congeners and metabolites of pesticides DDT, chlordane, hexachlorocyclohexane, and hexachlorobenzene. PCBs and pesticide metabolites were evaluated individually and summed by degree of chlorination and parent compound, respectively. Odds ratios (OR) and 95% confidence intervals (CI) were computed using conditional logistic regression per specified increase in lipid-adjusted concentration. We additionally stratified analyses by birth cohort (1923–1932, 1933–1942, 1943–1957).Increasing concentration of DDT metabolites (ORper 1000 ng/g = 0.80, 95%CI = 0.66–0.98) was inversely associated with thyroid cancer. Associations for PCBs were null or in inverse direction. We observed interactions for total PCBs, moderately-chlorinated PCBs, and chlordane metabolites with birth cohort (p ≤ 0.04). Among participants born 1943–1957, total PCBs (ORper 100 ng/g = 1.25, 95%CI = 1.00–1.56), moderately-chlorinated PCBs (ORper 100 ng/g = 1.31, 95%CI = 1.01–1.70), and chlordane metabolites (ORper 10 ng/g = 1.78, 95%CI = 1.09–2.93) were positively associated with thyroid cancer. For individuals born before 1943, associations were generally null or in the inverse direction.Emissions of PCBs and OC pesticides varied over time. Different risk patterns by birth cohort suggest the potential importance of timing of exposure in thyroid cancer risk. Further evaluation of these associations is warranted.First study of pre-diagnostic organochlorine compounds in serum and thyroid cancer.p,p′-DDE (DDT metabolite) inversely associated with thyroid cancer.Birth cohort may be an effect modifier.Some PCBs associated with thyroid cancer in youngest birth cohort.Chlordane metabolites associated with thyroid cancer in youngest birth cohort.