- The diagnosis and management of ependymoma may be challenging when there is a comorbidity of ependymoma and Parkinson's disease (PD). We report the first case to demonstrate unusual clinical and pathological features of an ependymoma associated with PD. A 77-year-old male with a history of PD had brain magnetic resonance imaging (MRI) that showed signal abnormalities in the right temporal lobe, most consistent with a low-grade glioma. He underwent an imaging-guided resection of that lesion, which pathological examination revealed mild hypercellularity with gliosis but no neoplasm, as well as Lewy bodies (LBs) and α-synucleinopathy in the temporal cortex compatible with advanced PD. Follow-up MRI exhibited tumor-like progression of signal abnormalities in that brain region. Twenty-nine months after the first resection, a head computerized tomography scan disclosed an obvious mass centered in the right temporal lobe. A second resection was performed for the mass, which pathological examination revealed an ependymoma with focal anaplasia and additional unusual features including an infiltrative growth pattern and intermixed α-synuclein positivity with electron microscopy finding of LB-like inclusions. Our observation suggests that an ependymoma in the patient with PD may present with unusual features possibly due to altered tumorigenesis and disease progression associated with α-synucleinopathy.