Background: Spinal cord involvement of primary central nervous system lymphoma (PCNSL) is rare in a young immunocompetent patient and can be misdiagnosed as an inflammatory demyelinating disease (IDD) of the central nervous system. Case report: We report a case of PCNSL mimicking IDD in a previously healthy 46-year-old man with weakness in both hands for 1 week. Magnetic resonance imaging (MRI) of the cervical spinal cord revealed contrast-enhancing intraparenchymal and leptomeningeal lesions in the cervical spinal cord and medulla oblongata. Cerebrospinal fluid analysis revealed pleocytosis (37/mm3). The patient’s symptoms and lesions improved with corticosteroid treatment. However, he developed semicomatose mentality 5 months later. Brain MRI, ventricular biopsy, and 18F-flurodeoxyglucose positron emission tomography/computed tomography confirmed PCNSL. The patient deceased 3 months later, despite high-dose methotrexate chemotherapy. Conclusion: Persistent gadolinium-enhancing MRI lesions along the ventricular regions and spinal leptomeninges could differentiate PCNSL involving the spinal cord from IDD in the early stages of the disease.