Abstract: Background and Objective: Estrogen Receptor (ER) expression promotes the resistance of breast cancer cells to chemotherapeutic agents via mechanism involving regulation of the B-cell lymphoma 2 (BCL-2) proto-oncogene. Overexpression of BCL-2 is commonly found in various types of cancers, including breast cancer. The BCL-2 expression might predict the patient’s response to selected chemotherapies. The aim of this study was to investigate the association between Estrogen Receptor α (ERα) and BCL-2 mRNA expression and the clinical response to neoadjuvant chemotherapy in breast cancer. Materials and Methods: This was a longitudinal study of breast cancer patients who underwent chemotherapy using a cyclophosphamide-adriamycin-5-FU regimen. Detection of BCL-2 and ERα mRNA expression in tissue samples was conducted using quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). Evaluation of the clinical response to chemotherapy was assessed using Response Evaluation Criteria in Solid Tumor (RECIST). Statistical analysis was performed using t-test and Pearson correlation methods. Results: The mean value of BCL-2 mRNA expression in the responsive group was 9.887±2.731. The mean value of BCL-2 mRNA expression in the non-responsive group was 10.017±2.122. The mean value of the responsive group was lower than that in the non-responsive group, but there was no significant correlation between BCL-2 mRNA expression and the clinical response to chemotherapy with an r-value was 0.378 and a p-value = 0.223 (p>0.05). The mean value of ERα mRNA expression in the responsive group was 10.144±1.945. The mean value of ERα mRNA expression in the nonresponsive group was 12.433±0.801. The mean value of the responsive group was lower than that in the nonresponsive group and there was a significant difference between the baseline ERα mRNA expression and that of the group that exhibited a clinical response to chemotherapy with a p-value = 0.006 (p>0.05). There was a negative correlation between ERα mRNA expression and the clinical response to chemotherapy with an r-value = -0.260, but this correlation was insignificant with a p-value = 0.166 (p>0.05). Conclusion: These results suggest that BCL-2 mRNA expression has a minimal influence in the clinical response of breast cancer to neoadjuvant chemotherapy, while elevated mRNA expression of ERα has some association with a lack of responsiveness to neoadjuvant chemotherapy.