To illustrate the potential of [I]-FP-CIT SPECT DaTSCAN® in investigating the progression of presynaptic dopaminergic degeneration in Huntington disease (HD), we performed a 2-year follow-up [I]-FP-CIT study on 4 HD patients, evaluating the SPECT imaging based on qualitative and semiquantitative analysis. The mean annual decline in [I]-FP-CIT uptake in caudate and putamen after 2 years of follow-up was 5.8% and 9.6%, respectively. Our findings suggest that [I]-FP-CIT SPECT is useful in investigating the progression of presynaptic dopaminergic degeneration in HD, and may be useful as a disease biomarker, providing an objective method for measuring the effectiveness of future neuroprotective therapies.