Here, we report for the first time a case of VHL-associated renal oncocytoma whose mtDNA genetic hallmark, a highly pathogenic mutation in respiratory Complex IV (CIV), was associated with the unique phenotype of undegraded, hyperhydroxylated, and dysfunctional HIF1α, suggesting that mtDNA mutations are potent modifiers in cancer. Here, VHL is linked to kidney oncocytoma.