Abstract: The distinct characteristics of mitochondrial DNA（mtDNA）， such as short length， simple molecular structure and high copy number， have made mtDNA an unique molecular tool for early tumor detection. Recently， circulating cell free mitochondrial DNA（ccfmtDNA） in blood has emerged as a noninvasive diagnostic and prognostic biomarker for many forms of solid tumors. In this review， we summarize the origin of ccfmtDNA in blood and the possible mechanism of the changes of ccfmtDNA levels. The possible diagnostic value of ccfmtDNA as a tumor marker is evaluated and the role of quantitative ccfmtDNA variations in neoplastic transformation and tumor progression is discussed.