Background: P-glycoprotein (Pgp), encoded by the multidrug resistance 1 (MDR1) gene, is an efflux transporter which plays an important role in pharmacokinetics. The current preliminary study was designed to determine associations between a germ-line polymorphism in the MDR1 gene with differentiated thyroid carcinoma (DTC). Materials and Methods: In the current case-control study, 60 differentiated thyroid cancers (DTC)- 45 papillary TC (PTC), 9 follicular TC(FTC) and 6 well-differentiated tumors of uncertain malignant potential (WDT-UMP) were examined. Results were compared to a healthy control group (n=58) from the same population. Genomic DNA was extracted from peripheral blood with EDTA and the target gene was genotyped by real-time PCR. Results: Carriers of the variant allele of MDR1 exon 26 polymorphism were at 2.8-fold higher risk of DTC than the control group (odds ratio [OR]: 0.3805, 95% confidence interval [Cl]: 0.1597-0.9065 (p> 0.046). Conclusions: Presented results suggest that the MDR1 3435TT genotype might influence risk of development of DTC and that the CC genotype might be linked to a poor prognosis. Large-scale studies are now needed to validate this association.