Purpose: Breast cancer is the most frequent female cancer, leading to relapse with distant metastasis of approximately one-third of patients. Cancer is usually considered a genetic disease involving mutations in nuclear DNA. However, genes, coding for mitochondrial proteins or regulatory molecules, are rarely under consideration. This study aimed to analyse 10 single nucleotide variants in POLG and TFAM genes and assess their association with tumour phenotype and disease outcome. Materials and methods: A total of 234 breast cancer patients were included in this study. Variations were determined with Real-Time PCR using TaqManVR probes. Results: We found that patients with POLG rs2307441 TT and CT genotypes had a lower probability for vascular invasion than those with CC genotype (p=0.001). Patients with POLG rs2072267 AG genotype were predisposed for progression compared with GG genotype (p=0.015). TFAM rs3900887 TT genotype was associated with a higher probability for positive oestrogen receptors (p=0.003) and lymphatic invasion (p=0.001) in comparison to AA genotype, patients with TT (p=0.000) were more likely to have positive lymph nodes. Conclusions: Our data suggest that variations in POLG and TFAM genes are important determinacies of tumour phenotype and disease outcome in breast cancer patients. [ABSTRACT FROM AUTHOR]