number of studies have been performed in the attempt to find molecular markers useful for the preoperative diagnosis of thyroid nodules. Most of these markers are tumour-expressed proteins (galectin-3, HBME-1, cytokeratin-19) or genes (BRAF V600E , RET/PTC, PAX-8/PPRc) that can be detected by immunohistological methods or by genetic analysis on biopsy specimens. 2–4 Particularly in areas with low iodine intake where goitre is more frequently multinodular, there is the issue of which nodule/s should be analysed by FNAC, because the analysis of all nodules is not always feasible or appropriate. The availability of a serological diagnostic method to detect the presence of a thyroid cancer would be very useful and highly desirable. Cancer is developed and sustained by genetic abnormalities that produce mutated or aberrantly expressed proteins. Mutated proteins and normal proteins inappropriately expressed may evoke a spontaneous immune response. Cellular immunity and antibody production against tumour molecules are defence tools of the host, whose efficacy against cancer development and progression is still to be fully understood. Spontaneous antibodies against tumour antigens are commonly produced and detectable in the serum of a large number of patients with cancer. Spontaneous antitumour antibodies can be evoked by mutated proteins present exclusively in tumours (tumour-specific antigens). More frequently, autoantibodies are evoked by aberrantly expressed proteins (tumour-associated antigens, TAAs) that become immunogenic because of their inappropriate expression. Some of these TAAs are molecules expressed during the ontogenesis and, thus in the postfoetal age, are present solely in the testis. For this reason, these antigens are named cancer–testis antigens (CTAs). TAA identification can be achieved by SEREX (serological analysis of recombinant cDNA expression libraries). The SEREX method was originally developed by Michael Pfreundschuh and colleagues in 1995. 5 Almost 3000 TAAs have been identified by this method and are listed in the Cancer Immunome Database (http://ludwig-sun5.unil.ch/CancerImmu nomeDB) developed by the Ludwig Institute of Cancer Research. These autoantibodies can be used as biomarkers for the diagnosis and prognosis of cancer and as serological markers of disease recurrence. The inconstant and dynamic nature of cancer makes a diagnostic test based on a single TAA inadequate. However, the lack of adequate sensitivity and specificity offered by a single TAA may be overcome by using a panel of TAAs where multiple autoantibodies are detected simultaneously. Detection of earlystage breast cancer by three TAA autoantibodies reached 770% sensitivity and 828% specificity. 6 A five TAAs-based test was able to discriminate between patients with early colorectal carcinoma and healthy controls, with sensitivities of 900% and specificities of 917%. 7 While TAA screening and search for the corresponding autoantibodies have been conducted for breast, prostate, lung, colon and many other cancers, very little has been conducted for thyroid cancer. The expression analysis of 13 selected CTAs demonstrated the presence of NY-ESO-1 in about 60% of sporadic medullary thyroid carcinomas and the presence of the corresponding antibody in 36% of patients. 8 Few other