A 35-year-old man underwent contrast-enhanced MRI and F-FDG PET/CT for acute peripheral paresthesia, vision loss, muscle weakness, and difficulty walking. T2-weighted MRI demonstrated multiple bright periventricular supratentorial and infratentorial white matter lesions, including 2 with nodularity. Both nodular lesions showed moderate focal FDG uptake (SUVmax, 6.9 in both cases). Cerebrospinal fluid analysis showed increased levels of immunocytes and oligoclonal antibody bands. A diagnosis of acute onset tumefactive multiple sclerosis was made.