The receptors for thyroid hormone (THR) and oestrogen (ESR) are prototypes of nuclear transcription factors that regulate the expression of target genes. Genetic alterations in the genes of these receptors were found to be involved in cancer development. In this study we investigated the association of one SNP (rs2228480, T594T) and one microsatellite marker (D6S440) within the ESR1 gene and a dinucleotide repeat (D17S2189) within the THRA gene, with thyroid cancer risk. A case-control association study was conducted with 299 healthy individuals and 106 patients with thyroid cancer. Genotypic and allelic frequencies for the dinucleotide repeat in the ESR1 gene were similar between thyroid cancer patients and controls. For the AC repeat in the THRA gene, a slightly significant difference was found for the genotype 18/20 between the two groups (P = 0.034), which suggests that alleles with less than 20 repeats might have a protective effect in thyroid cancer risk. For the SNP T594T, the A allele was much more prevalent in patients than in controls and was highly associated with the risk of thyroid cancer (OR: 4,56; IC: 3.23-6.44; P < 10(-18)) and seems to have an additive mode of action. In conclusion, our data suggest that the SNP T594T but not the D6S440 and D17S189 is associated with thyroid cancer risk.