Purpose: The aim of the study was to evaluate extrastriatal dopaminergic and serotonergic pathways in patients with Parkinson’s disease (PD) and dementia with Lewy bodies (DLB) using 123 I-FP-CIT SPECT imaging. Methods: The study groups comprised 56 PD patients without dementia, 41 DLB patients and 54 controls. Each patient underwent a standardized neurological examination and 123 I-FP-CIT SPECT. Binding in nigrostriatal and extrastriatal regions of interest was calculated in each patient from spatially normalized images. The occipital-adjusted specific to nondisplaceable binding ratio (SBR) in the different regions was compared among the PD patients, DLB patients and controls adjusting for the effects of age, sex, disease duration and serotonergic/dopaminergic treatment. Covariance analysis was used to determine the correlates of local and long-distance regions with extrastriatal 123 I-FP-CIT deficits. Results: Both PD and DLB patients showed lower 123 I-FP-CIT SPECT SBR in several regions beyond the nigrostriatal system, especially the insula, cingulate and thalamus. DLB patients showed significantly lower 123 I-FP-CIT SBR in the thalamus than controls and PD patients. Thalamic and cingulate 123 I-FP-CIT SBR deficits were correlated, respectively, with limbic serotonergic and widespread cortical monoaminergic projections only in DLB patients but exhibited only local correlations in PD patients and controls. Conclusion: PD and DLB patients both showed insular dopamine deficits, whereas impairment of thalamic serotonergic pathways was specifically associated with DLB. Longitudinal studies are necessary to determine the clinical value of the assessment of extrastriatal 123 I-FP-CIT SPECT. © 2019, Springer-Verlag GmbH Germany, part of Springer Nature.