Breast cancer is a serious and potentially lethal multi-factor disease among 40-50 aged women in bothdeveloped and developing countries. Also, various studies have pointed to roles of neurotransmitters like serotoninin development of cancers, through action on various types of receptors. This study was conducted to evaluateserotonin receptor (5HT2AR and 5HT3AR) genes expression in peripheral blood mononuclear cells (PBMCs)of breast cancer patients in comparison with the healthy people and in the MCF7 cell line. Peripheral bloodsamples were obtained from 30 patients and 30 healthy individuals. Total RNA was extracted from PBMCs andMCF-7 cells. and 5HT2AR and 5HT3AR were detected by RT-PCR techniques. Finally, serotonin receptor geneexpression variation in breast cancer patients and MCF-7 cells were determined by real time-PCR. This latterindicated significant promotion in expression of 5HT3AR and 5HT2AR in PBMCs in breast cancer patientsbut expression of 5HT2AR in the MCF-7 cell line was significantly decreased. In conclusion, after performingcomplimentary tests, determine of gene expression changes in serotonin receptors (5HT2AR and 5HT3AR) maybe useful as a new approach in treatment of breast cancer based on use of antagonists.