Background: Our studies over recent years have focused on some new ideas concerning the pathogenesis for the orbital reaction that characterizes Graves’ ophthalmopathy namely, that there are antigens expressed by thyroid tissue and orbital tissue where they are targeted by autoantibodies and/or sensitized T cells, leading to orbital inflammation. While this has been well studied for the thyroid stimulating hormone-receptor, the possible role of another major thyroid antigen, Thyroglobulin (TG), has been largely ignored. Methods: We identified novel variant 1623 A/G single nucleotide polymorphism (SNP) (rs180195) in the promoter of TG gene associated with autoimmune thyroid disorders. We genotyped the TG SNPs rs2069566, rs2076739, rs121912646, rs121912647, rs121912648, rs121912649, rs121912650, rs137854433, rs137854434, and rs180195 by MassARRAY SNP analysis using iPLEX technology in a cohort of 529 patients with thyroid autoimmunity with and without ophthalmopathy, and controls. Results: We showed that variant 1623 A/G SNP (rs180195) in the promoter of TG gene is a marker for thyroid autoimmunity, but not for ophthalmopathy. We showed that there was a significant difference in the distribution of the major allele (G) vs minor allele (A) in patients with Hashimoto’s thyroiditis (HT). In HT the wild-type (GG) genotype was less common. We showed that the genotypes homozygous AA and heterozygous GA rs180195 SNP in the promoter of TG gene were more closely associated with thyroid autoimmunity than the wild-type (GG) polymorphism, and are thus, markers of autoimmunity. Conclusion: rs180195 SNP was previously identified by Stefan et al independently of us, who showed that this TG SNP predisposed to autoimmune thyroid diseases. However, this is the first study to explore the association between TG SNPs and HT. Our findings support the notion that the thyroid and orbital disorders are not part of the same disease, ie, “Graves’ disease” or “Hashimoto’s disease”, but separate autoimmune disorders.