Background: The incidence of thyroid cancer in patients treated operatively for thyroid disease has been historically low (<5%). Previous series have not specifically addressed cancer rates in both euthyroid and hyperthyroid patients. This study examined cancer frequency in patients referred for removal of benign thyroid disease in a multi-institutional series. Study Design: A total of 2,551 patients underwent thyroidectomy at 3 high-volume institutions. Indeterminate/malignant fine-needle aspiration diagnosis was excluded (n = 1,028). Cancer cases were compared among 1,523 patients with Graves' disease (n = 264), nodular goiter (n = 1,095), and toxic nodular goiter (n = 164). Fisher's exact test, chi-square test, Wilcoxon rank sum, Kruskal-Wallis nonparametric t-tests, and multivariable logistic regression were used. Results: Overall, 238 (15.6%) cancers were recorded: Graves' disease (6.1%), nodular goiter (17.5%), and toxic nodular goiter (18.3%). Cancer rates were significantly different among these groups (p < 0.01) and significantly higher in nodular goiter and toxic nodular goiter vs Graves' disease (p < 0.01); no significant differences in cancer rates were noted among institutions. Overall, 275 patients had thyroiditis (18%). There was a significant association with younger age, male sex, nodular thyroids, and cancer (p < 0.05). Presence of thyroiditis or performance of preoperative fine-needle aspiration was not associated with cancer. Mean cancer size was 1.1 cm (46% >0.5 cm; 39% >1 cm). Most patients underwent total thyroidectomy (80%). Conclusions: These data confirm higher than expected incidental thyroid cancer rates (15.6%) in the largest multi-institutional surgical series to date. Nodular thyroids, males, and young patients were more likely to harbor incidental carcinoma. These data support consideration of initial total thyroidectomy as the preferred approach for patients referred to the surgeon with bilateral nodular disease. © 2013 by the American College of Surgeons.