Abstract: Numerous somatic mutations in both the coding and control regions of mitochondrial DNA（mtDNA） have been extensively examined in human breast cancer in the past decades， underscoring that accumulation of mitochondrial defects and consequently contributing to cancer initiation and progression. This review outlines a wide variety of somatic mtDNA mutations identified in breast cancer and highlights recent advances in understanding the causal roles of mtDNA variations in neoplastic transformation and tumor progression. In addition， it briefly illustrates how mtDNA alterations active mitochondria-to-nucleus retrograde signaling so as to modulate and promote malignant phenotypes in cancer cells. The present state of our knowledge regarding how mutational changes in the mitochondrial genome could be used as a diagnostic biomarker for early detection of breast cancer and as a potential target in the development of new therapeutic approaches is also discussed.