Hashimoto’s thyroiditis (HT) is the most common autoimmune disease among the causes of human hypothyroidism. HT is characterized by cellular immunity through infiltration of the thyroid gland by T and B lymphocytes, but also by humoral immunity through the production of specific antibodies. the co-occurrence of HT with papillary thyroid cancer (PTC) suggests a possible immunological association between the two diseases. Two researchers from the Department of Endocrinology, University of Düsseldorf, Germany, present a review of the potential mechanisms leading to the simultaneous occurrence of HT and PTC, recently published in the journal Trends Endocrinol Metab, published by Cell. There are several unanswered questions: 1. Do thyroid malignancies occur in spite of the immune response? 2. Does autoimmune thyroiditis occur as a result of an anti-tumor immune response? 3. Does autoimmune thyroid disease occur because of a pre-existing antitumor immune response? 4. Thyroid peroxidase and thyroglobulin: are they both target antigens of the humoral and cellular immune responses to Hashimoto’s thyroiditis and papillary thyroid cancer? 5. Hashimoto’s thyroiditis and papillary thyroid cancer: are they two aspects of the body’s immunity? The thyroid is the organ most susceptible to autoimmune attack and Hashimoto’s thyroiditis (HT) is the most common thyroid autoimmune disease. The key factor in the pathogenesis of HT is a decreased immune tolerance to the thyroid gland. In response to the first stimulation by environmental and other factors such as iodine intake, the earlier thyroid-tolerant immune cells are activated and thus lose their tolerance to the thyroid gland. Subsequently leukocytes infiltrate the thyroid tissue and promote the development of an autoimmune response. In fact, HT is defined as a devastating tissue-specific autoimmune disease with antithyroglobulin antibodies (TgAb) and antithyroid peroxidase antibodies (TPOAb). The result is that HT often leads to hypothyroidism, as evidenced by a deficiency of thyroid hormones (triiodothyronine (T3) and thyroxine (T4)) and elevated thyroid stimulating hormone (TSH) levels. Because TSH induces thyroid cell hyperplasia, elevated TSH may potentially increase the risk of thyroid cancer. An association between papillary thyroid cancer (PTC) and serum TSH levels has been demonstrated. Lowering TSH levels with levothyroxine may reduce clinically detectable PTC. Differentiated thyroid cancer is one of the most common endocrine tumors invading the thyroid gland, and PTC is the most common of these. Differentiated thyroid cancer accounts for approximately 90% of all thyroid cancers and is often inert with a good prognosis (10-year survival rate over 90%) unless metastases occur or radioactive iodine therapy or surgery cannot be used. The incidence of differentiated thyroid cancer has increased over the past 30 years from 3.6/100,000 person-years in 1973 to 12.2/100,000 in 2010. the reasons for this increase may be varied and not fully understood, one explanation being the increase in incidental microadenomas due to increased sensitivity of diagnostic tools. The association between HT and PTC has been discussed for a long time, with contradictory evidence, and PTC often occurs in patients with autoimmune thyroiditis, raising the question: how does malignancy occur in immune responsive thyroid tissue? In this article we review recent studies that have improved the understanding of the cellular and humoral immune mechanisms of HT, with particular emphasis on the immunologic link between autoimmune disease and thyroid cancer.