Objective: Breast cancer is known as the most prevalent cancer among women and the second most common cancer in the world. Different studies mentioned the chemorespon-siveness potential of breast cancer among solid tumors. Though resistance against chemotherapy drugs is a major problem in cancer therapies that could lead to treatment failure. Multidrug resistance proteins (MDRs) are one of the main members of transporting protein that play a crucial role in pharmacokinetics. P-glycoprotein (P-gp) is the product of MDR1 gene, which is responsible for absorption, distribution, metabolism, excretion (ADME), and drug-drug interaction (DDI) of drugs in humans. The role of MDR1 3435C>T variation on alteration of P-glycoprotein expression and its contribution in risk of breast cancer is proven. Therefore, we decided to examine the role of 3435C>T polymorphism on breast cancer risk in Mazandaran, Iran. Patients and Methods: A case-control study involving 196 breast cancer patients and 98 healthy subjects was conducted. Genomic DNA was isolated from the whole blood sample by a column-based method. The polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP) technique was used for genotyping of MDR1 3435C>T polymorphism. Results: Distributions of the TT, CT, and CC genotypes of MDR1 were 34.7, 50, and 15.3%, respectively, in controls, and 32.2, 48.9, and 19% in breast cancer patients. There were no significant differences between the cases and controls. Conclusions: Genetic polymorphism of MDR1 C3435T was not found to be associated with increased risk of breast cancer. Further studies on different larger population are needed to confirm these data.