BACKGROUND Mitochondrial DNA (mtDNA) mutations are considered as a possible primary cause of age-associated neurodegenerative disorders like Parkinson's disease (PD). OBJECTIVE To analyze, along the whole mtDNA sequence of PD patients, the presence of non-reference alleles compared to reference alleles, as defined in the revised Cambridge Reference Sequence (rCRS). METHODS mtDNA was extracted from whole blood of PD and control groups, and was sequenced using a chip-based resequencing system. RESULTS 58 nucleotide positions (np) exhibited a different allelic distribution in the two groups; in 81% of them the non-reference alleles were over-represented in PD patients, similar to findings reported in patients with Alzheimer's disease, albeit in reduced proportion. Closer analysis of the 58 np in PD group showed that they were characterized by low-level heteroplasmy, and that the nucleotide substitutions determined an amino acid change in 84% of cases. CONCLUSIONS These results suggest that mtDNA allelic changes are increased in PD and that age-related neurodegenerative diseases could share a common mechanism involving mtDNA.