OBJECTIVES: To provide an automated classification method for degenerative parkinsonian syndromes (PS) based on semiquantitative 123I-FP-CIT SPECT striatal indices and support-vector-machine (SVM) analysis. METHODS: 123I-FP-CIT SPECT was performed at a single-center level on 370 individuals with PS, including 280 patients with Parkinson's disease (PD), 21 with multiple system atrophy-parkinsonian type (MSA-P), 41 with progressive supranuclear palsy (PSP) and 28 with corticobasal syndrome (CBS) (mean age 70.3 years, 47% female, mean disease duration at scan 1.4 year), as well as 208 age- and gender-matched control subjects. Striatal volumes-of-interest (VOIs) uptake, VOIs asymmetry indices (AIs) and caudate/putamen (C/P) ratio were used as input for SVM individual classification using fivefold cross-validation. RESULTS: Univariate analyses showed significantly lower VOIs uptake, higher striatal AI and C/P ratio for each PS in comparison to controls (all p < 0.001). Among PS, higher degree of striatal impairment was observed in MSA-P and PSP, while CBS showed moderate uptake reduction and higher AI. Binary SVM classification showed 92.9% accuracy in distinguishing PS from controls. Classification based on each binary combination of PS ranged 62.9-83.7% accuracy with the most satisfactory results when separating CBS from the other PS. Sensitivity and specificity values were high and balanced ranging from 60 to 80% for all analyses with > 70% accuracy. Overall, striatal AI and C/P ratio on the more affected side had the highest weighting factors. CONCLUSION: Semiquantitative 123I-FP-CIT SPECT striatal evaluation combined with SVM represents a promising approach to disentangle PD from non-degenerative conditions and from atypical PS at the early stage.