Substantia nigra (SN) hyperechogenicity can be demonstrated by transcranial ultrasonography (TCS) as a typical, stable finding in about 90% of patients with Parkinson's disease (PD). SN hyperechogenicity is also observable in about 10% of normal healthy controls, irrespective of age. TCS of the SN is likely to be useful for the differential diagnosis of PD and related disorders, because SN hyperechogenicity is observed less frequently in patients with atypical parkinsonism, such as multiple system atrophy and progressive supranuclear palsy. Unfortunately, in Japanese patients, the rate of successful recording of the SN by TCS decreases prominently with advancing age. particularly in females. The cause of SN hyperechogenicity remains undetermined. However, there is a hypothetical concept that SN hyperechogenicity is a biomarker of vulnerability of the nigrostriatal dopaminergic system associated with increased iron levels in the SN. We propose that TCS is a useful tool for not only the clinical evaluation of patients with PD or related disorders, but also the preclinical evaluation of subjects at risk of developing PD. We hope that this brief review will contribute to a better understanding of the potential of TCS of the SN in patients with PD.