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Background and objective: Breast cancer is the extreme widespread carcinoma in women and considered to be as the second major reason of demise in human being. Tumor markers are particularly helpful in controlling medicament also in identification of metastasis and early discovery of returning. The present research was designed to examine the plasma levels, diagnostic and differentiating utilities of vascular endothelial growth factor A (VEGF A) and macrophage-colony stimulating factor (M-CSF) in Iraqi women with breast cancer (BC), benign breast tumor women , well control women and to compare their results with that of routine used one, the CA 15-3. Subjects and Techniques:The present research was executed at the Department of Biochemistry, College of Medicine – University of Baghdad and at the Central Office for the Soon Disclosure of Breast cancer at Baghdad Teaching Hospital for Oncology/Medical City, over the interval of February 2017 until the end of November 2017. Eighty-eight Iraqi women were involved in the study; 38 women with primary breast cancer (BC), 25 women with benign breast tumor and 25 well control women. BC women were also classified in respect to their stage of cancer; stage I, II, and III. Seeking involved plasma measuring of VEGF A, M-CSF and CA 15-3 levels in whole enclosed women by using enzyme-linked immunosorbent assay (ELISA) technique. Results: The results indicate significant increase of VEGF A, M-CSF, and CA 15-3 in BC women in comparison to benign tumor and healthy women (p=0.001), with non-significant differences between benign tumor and healthy women. However, plasma VEGF A has the highest diagnostic utility (AUC=0.958) in differentiation between women with BC from those with benign tumor or healthy ones compared with M-CSF (AUC=0.662) and CA 15-3 (AUC=0.0.934). In addition, plasma VEGF A has the best ability (AUC=0.877) in differentiating early stage of BC from benign tumor or healthy women in comparison to CA 15-3 (AUC=0.807). Plasma M-CSF has the poor efficiency in such clinical application (AUC=0.68). Moreover, plasma VEGF A was suggested to be the accurate one in differentiating women with benign tumor from healthy control women.Conclusion:The present study found that plasma VEGF A has superior diagnostic utility of early BC and differentiating efficiency from benign tumor and healthy women of that of routine used one plasma CA-15-3. In addition, VEGF A was the best one in discriminating of benign tumor from control women. Plasma M-CSF was the poor one in such clinical uses. The replacement of plasma VEGF A instead of CA 15-3 in assessment of early BC and benign tumor is required and could be to reduce the biopsy.