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A 75-year-old man, undergoing treatment for metastatic prostate cancer with a novel cancer cell vaccine, presented with a 4 week history of poor balance, gait disturbance and cognitive decline. Blood tests including HIV and onconeuronal and voltage gated potassium channel antibodies were normal. Computed tomography and two magnetic resonance images of the brain showed possible non-specific meningeal or vascular enhancement. Two cerebrospinal fluid analyses, including cytology, were negative, other than six lymphocytes in the former. Despite intravenous aciclovir and dexamethasone the patient deteriorated over 16 days, with worsening confusion and involuntary movements, and died. Postmortem examination showed that the leptomeninges overlying the brain and spinal cord were diffusely infiltrated by a melanocytosis with a focal area of melanomatosis. Moreover, there were two sites of metastases of a highly malignant clone present in the pulmonary parenchyma.