A 38-year-old woman was diagnosed with cutaneous anaplastic T-cell lymphoma that proved refractory to methotrexate, bexarotene, denileukin diftitox, interferon γ-1b, interferon α-2b, vorinostat, and pralatrexate. She was therefore started on the newly approved monoclonal anti-CD30 antibody brentuximab vedotin. Treatment with brentuximab 1.8 mg/kg IV every 3 weeks quickly led to disappearance of her cutaneous tumors. The day after her second brentuximab infusion she developed word-finding difficulties and unsteady gait. Due to further neurologic deterioration, she was admitted to an outside hospital. Brain MRI revealed multifocal enhancing white matter lesions throughout bilateral cerebral hemispheres and posterior fossa (figure, A-C). Brain biopsy was performed 15 days after her last brentuximab dose to rule out metastases and she was diagnosed with progressive multifocal leukoencephalopathy (PML) (figure, J). The patient was discharged home with hospice care. Upon discharge, she was started on prednisone 50 mg daily to help treat her eczema. Her family brought her to our clinic for a second opinion.