Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are thought to be part of a spectrum: both have a clinical profile including symptoms associated with dopaminergic and serotonergic loss, yet few imaging studies have focused on serotonergic neurodegeneration in both disorders. We aimed to study degeneration of terminals with dopamine and serotonin transporter (DAT and SERT, respectively) in patients with early-stage PD and DLB relative to healthy controls, using 123 I-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane ( 123 I-FP-CIT) single photon emission computed tomography (SPECT). We conducted region of interest (ROI) and voxel-based analyses on 123 I-FP-CIT SPECT scans. Using the cerebellum as a reference region, we determined binding ratios (BRs) for bilateral ROIs in the DAT-rich striatum (head of the caudate nucleus and posterior putamen) and SERT-rich extrastriatal brain regions (thalamus, hypothalamus and hippocampus). We compared BRs in PD and DLB patients with BRs in healthy controls (all groups: n = 16). Both PD and DLB patients had lower striatal 123 I-FP-CIT BRs than healthy controls for the bilateral caudate head (PD—left: F(1,29) = 28.778, P <.001, ω 2 = 0.35; right: F(1,29) = 35.338, P <.001, ω 2 = 0.42; DLB—left: F(1,29) = 28.241, P <.001, ω 2 = 0.31; right: F(1,29) = 18.811, P <.001, ω 2 = 0.26) and bilateral posterior putamen (PD—left: F(1,29) = 107.531, P <.001, ω 2 = 0.77; right: F(1,29) = 87.525, P <.001, ω 2 = 0.72; DLB—left: F(1,29) = 39.910, P <.001, ω 2 = 0.48; right: F(1,29) = 26.882, P <.001, ω 2 = 0.38). DLB patients had lower hypothalamic 123 I-FP-CIT BRs than healthy controls (F(1,29) = 6.059, P =.020, ω 2 = 0.12). In the voxel-based analysis, PD and DLB patients had significantly lower striatal binding than healthy controls. Both PD patients in the early disease stages and DLB patients have reduced availability of striatal DAT, and DLB patients lower hypothalamic SERT compared with healthy controls. These observations add to the growing body of evidence that PD and DLB are not merely dopaminergic diseases, thereby providing additional clinicopathological insights.