Breast cancer is a leading cause of cancer-related deaths in women worldwide and most common cancer among females in Egypt. In this study, we evaluated the level of ccfnDNA & mtDNA as a biomarker in the peripheral blood for distinguishing between malignant and non malignant breast disease using the highly sensitive real time PCR Taqman assay. There was significant elevation of ccfDNA & mtDNA level in malignant cases in relation to non malignant cases with statistically significant association between ccfDNA & mtDNA level and grade of the tumor, tumor stage, lymph node status, the hormonal receptor status and expression of HER-2 neu .