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A number of studies have demonstrated the presence of mitochondrial DNA (mtDNA) mutations in cancer cells. In this article, we review mitochondrial genomic aberrations reported in solid tumors of the breast, colon, stomach, liver, kidney, bladder, head/neck, and lung. The tantalizing association of tumors with mtDNA mutations implicates these mutations in the process of carcinogenesis. Alterations in expression of mtDNA transcripts in a variety of cancer types are also reviewed. In solid tumors, elevated expression of mtDNA-genes coding for subunits of the mitochondrial electron respiratory chain may reflect mitochondrial adaptation to perturbations in cellular energy requirements. The role of mtDNA mutations and altered expression of mitochondrial genes in carcinogenesis is discussed. Mitochondrial DNA mutations can initiate a cascade of events leading to a continuous increase in the production of reactive oxygen species (persistent oxidative stress), a condition that probably favors tumor development.