The inhibition of tumor growth induced by blocking DHODH supports targeting pyrimidine synthesis as a potential widely applicable therapeutic approach.<h4>Significance</h4>Mitochondrial complexes III and IV promote tumor progression by supporting de novo pyrimidine synthesis, requiring cancer cells devoid of mitochondrial DNA to recruit mitochondria from source cells to restore respiration in order to form tumors. This evidence concerns the gene DHODH and cancer.