BACKGROUND Although advances in treatment have permitted patients with systemic lupus erythematosus (SLE) to live longer, the rates of several types of cancers in these patients appear to be increasing. OBJECTIVE We used a prospective study to investigate the prevalence and features of thyroid cancer in SLE patients. METHODS The prevalence of thyroid cancer in 153 unselected SLE patients was compared with that in two population-based, gender- and age-matched control groups: 1) 459 subjects from an iodine-deficient area (iodine-deficient control) and 2) 459 subjects from an iodine-sufficient area (iodine-sufficient control). Thyroid function was assessed by measuring circulating thyroid hormones and autoantibodies, thyroid ultrasonography, and where necessary, fine-needle aspiration cytology. RESULTS The levels of circulating TSH, and anti-thyroglobulin and anti-thyroperoxidase antibodies were significantly higher in SLE patients (P < 0.001 for all). In addition, patients with SLE also exhibited a higher prevalence of hypothyroidism (P < 0.001). Five cases of papillary thyroid cancer were detected among SLE patients, whereas no cases were observed among iodine-deficient controls (P = 0.001), and only one case was observed among iodine-sufficient controls (P = 0.001). Among SLE patients with confirmed thyroid cancer, 80% showed evidence of thyroid autoimmunity, whereas only 31% of SLE patients without thyroid cancer exhibited evidence of thyroid autoimmunity (P = 0.02). CONCLUSIONS These data suggest that the prevalence of papillary thyroid cancer in SLE patients is higher than in age-matched controls, particularly in patients with thyroid autoimmunity. Consequently, careful thyroid surveillance is recommended during the follow-up of these patients.