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Background The relationship between thyroid autoimmunity and cancer is still uncertain. Patients We approached this issue in 570 consecutive patients submitted to thyroidectomy for an indeterminate nodule on cytology. Thyroid autoimmunity was defined as positivity of circulating thyroid autoantibodies (TAb), autoimmune hypo- or hyperthyroidism, thyroid hypoechogenicity on ultrasound, and lymphocytic infiltration on histology. Results TAb were found in 122/570 (21·4%), hypoechogenicity in 115/570 (20·1%), and lymphocytic infiltration in 117/570 (20·5%) of patients. The three features of thyroid autoimmunity were highly concordant: hypoechogenicity was observed in 71/448 (15·8%) patients with negative TAb and in 44/122 (36%) with positive TAb ( P < 0·0001); lymphocytic infiltration was found in 53/448 (11·8%) patients with negative TAb and in 64/122 (52·4%) with positive TAb ( P < 0·0001); hypoechogenicity on ultrasound was observed in 73/453 (16·1%) patients without, and in 42/117 (35·9%) with lymphocytic infiltration ( P < 0·0001). None of these parameters was associated with malignancy. TAb were found in 32/135 (23·7%) patients with carcinoma and in 90/435 (20·6%) with a benign lesion ( P = NS); hypoechogenicity was observed in 26/135 (19·2%) patients with carcinoma and in 89/435 (20·4%) patients with benign lesions ( P = NS); lymphocytic infiltration was present in 28/135 (20·7%) patients with carcinoma and in 89/435 (20·4%) with benign lesions ( P = NS). The frequency of cancer in 11 patients with clinically overt thyroid autoimmune disease did not differ from that observed in the whole study group. Conclusion In this group of patients with indeterminate thyroid nodules at cytology, clinical and pathological criteria of thyroid autoimmunity were strongly concordant and not associated with malignancy. [ABSTRACT FROM AUTHOR]