In vitro gamma-radiation-induced chromatid breaks per cell (b/c) in lymphocytes may be associated with risk of papillary thyroid cancer (PTC). This pilot case-control study involved 106 patients with thyroid disease (57 with PTC and 49 with benign thyroid disease) and 105 cancer-free matched controls. Multivariate logistic regression analyses identified that an elevated gamma-radiation-induced b/c value was a risk factor for PTC (adjusted odds ratio = 4.54; 95% CI, 2.07-9.95), and a dose-response relationship was evident when the b/c values were categorized into tertiles. High levels of chromatid breaks induced by gamma-radiation may constitute an independent risk factor for PTC, but further study is needed.