Background: Some but not all reports, particularly those of a retrospective nature, have noted an increased risk of carcinoma in thyroid nodules in patients with Hashimoto's thyroiditis (HT). Thyroid cancer (TC) in patients with HT, however, have been reported to have a better prognosis. In the presence of HT, the ultrasonography (US) appearance of the thyroid gland might vary greatly, making it more difficult to differentiate between benign and malignant nodules. The aim of this study was to determine if there is an association between TC and HT and to determine if the US and histopathologic characteristics of malignant nodules in patients with and without HT are similar. Methods: Six hundred thirteen patients who underwent total thyroidectomy between 2005 and 2008 for nodular goiter were included in this study. The preoperative US characteristics and postoperative histopathologic features in patients with and without HT were compared. The diagnosis of HT was based on histopathologic features. Results: Ninety-two patients had HT. The prevalence of TC in the HT patients was 45.7%. In contrast, it was 29% in patients without HT (p = 0.001). The prevalence of HT in the patients with TC was 21.8% and in patients without TC was 11.9% (p = 0.001). The rate of incidental TC, defined as TC identified during surgery or following histopathologic examination of permanent sections despite preoperative benign cytology results, was higher in patients with HT (33.3%) than in those without (13.0%) HT (p = 0.004). The US characteristics of papillary thyroid carcinoma, which included number of nodules, echogenity, echoic texture, microcalcifications, macrocalcifications, halo sign, and regularity of margins, were similar in the group with HT compared with the group without HT. When the histopathologic characteristics of papillary thyroid carcinoma in patients with and without HT were compared, again there was no significant difference. Conclusions: We suggest that there is an association between HT and TC, and HT may predispose to the development of TC. This indicates the need for close observation of neoplastic changes in patients with HT. Nevertheless, the presence of HT seems to have no effect on the US and histopathologic characteristics of malignant nodules in TC patients. This finding may indicate that evaluation of nodules and initial treatment of TC in these patients does not require different management. © 2010 Mary Ann Liebert, Inc.