Mutations in the mitochondrial genome have been reported as biomarkers for the detection of cancer. Hallmarks of cancer development include the accumulation of genetic alterations in the mitochondrial and nuclear genomes. Damage to mitochondria affects energy metabolism, generation of reactive oxygen species, apoptosis, cell growth and other processes that contribute to the neoplastic process. Furthermore, mitochondrial DNA mutations occur frequently in cancer. Little work has been done to link a pathway between mitochondrial mutations and cancer etiology. Volumes of work have been reported on the association of mitochondrial mutations and almost all types of cancer including the use of body fluids for early detection. This review examines the measurement of mitochondrial mutations for the application of detecting human tumor tissue.