Abstract Introduction: Uncoupling proteins (UCPs) are a family of inner mitochondrial membrane proteins whose function is to allow the re-entry of protons to the mitochondrial matrix, to decrease membrane potential and production of reactive oxygen species (ROS). Due to their pivotal role in the intersection between energy efficiency and oxidative stress, UCPs are being investigated for a potential role in cancer researches .UCP2 proteins functions in a variety of cell types as a sensor of mitochondrial oxidative stress and may be activated by superoxide or subsequently formed lipid peroxidation products. The ability of cancer cells to regulate ROS levels contributes greatly to autonomous growth, the evasion of apoptosis, and other hallmark characteristics of adaptation. Thus, UCP2 activity, a negative regulator of ROS, should be related to cancer development or progression. Over expression of UCP2 has been shown in different cancers. However, until now the role of UCP2 in breast cancers is not well understood. The aim of the current research study was to evaluate the association of UCP2 expression and clinic-pathological features in Iranian breast cancer patients. Patients and Methods: Thirty five breast cancer patients who referred to the National Cancer Institute (NCI) at Imam Khomeini Hospital Complex, Tehran, Iran from Oct. 2007 to Oct. 2009 were contributed in this study. The pathologic changes in tumor samples were determined by two expert pathologists. Each specimen was immediately frozen following resection and stored at -80°C until subjected to RNA extraction. UCP2 expression was analyzed by relative PCR method was performed in subjects. Results and Conclusion: The expression of UCP2 mRNA in 31 out of 35 breast cancer tissue samples and its adjacent tissue samples was determined. The expression level of UCP2 mRNA was about four-fold higher in 58% of breast cancer tissue samples than its adjacent tissue samples. The correlation between UCP2 expression and clinical pathological features of breast cancer including tumor stage, histological grade, estrogen receptor status, progesterone receptor status, Her-2/neu status, lymph node status, P53 status and metastasis status were analyzed. There was not a significant association between expression levels of UCP2 and clinical pathological features (P> 0.05). However, there was a significant association between the UCP2 expression and tumor size (P< 0.028). This finding may significantly play a role in the etiology of tumor development of breast cancer. Furthermore, our finding may be lead to determine whether UCP2 expression is an effective factor for tumor development in breast cancer cells so, targeted therapy drugs to impact this gene expression in the nucleus may be useful. Further studies are warranted to confirm these findings. Note: This abstract was not presented at the meeting. Citation Format: Neda Maraghechi, Massoud Ghaffarpour, Golna Asaadi Tehrani. Overexpression of UCP2 is associated with tumor progression in Iranian breast cancer patients. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4325. doi:10.1158/1538-7445.AM2014-4325