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A man in his early 50s presented with progressive numbness of the right hand and arm. His medical history included focal segmental glomerulosclerosis and a kidney transplant 10 years earlier. Neurological examination showed decreased pinprick sensation in C6–C8 dermatomes and mild weakness in corresponding myotomes. Cervical spine MRI revealed a rim-enhancing intramedullary lesion at C1 with restricted diffusion and surrounding oedema extending to C3. Initial differentials included lymphoma, particularly post-transplant lymphoproliferative disorder (PTLD), and pyogenic abscess. Spinal cord biopsy was deferred due to high surgical risk. The patient was treated with intravenous antibiotics, corticosteroids and reduced immunosuppression. MRI initially showed improvement, but symptoms and lesion size worsened after steroid taper. Tissue biopsy from C1–C2 spinal cord lesion confirmed CD20-positive EBER-negative lymphoid cells, establishing the diagnosis of PTLD. He commenced rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone chemotherapy but developed septic shock followed by multiorgan failure. He died 2 weeks later. This case highlights an unusual presentation of central nervous system PTLD as an isolated cervical spinal cord mass, posing diagnostic and therapeutic challenges.