Primary central nervous system lymphoma (PCNSL) can be associated with preceding demyelinating pseudotumoral brain lesions. The 'sentinel' demyelinating lesions recede spontaneously or with corticosteroid, and are followed by development of PCNSL typically within 12 months. This report describes a 29 year-old post-partum woman who developed PCNSL 4 years after a biopsy-proven pseudotumoral demyelinating episode. She presented with focal seizures in February 2005. She subsequently developed hemiparesis and raised intracranial pressure. MRI showed two contrast enhancing lesions in the right frontal lobe, which were hypermetabolic on (18)F-FDG PET. A provisional diagnosis of tumefactive multiple sclerosis was made. Symptoms recurred despite multiple courses of high dose corticosteroid. Brain biopsy confirmed large B-cell non-Hodgkin's lymphoma. This patient illustrates the importance of considering PCNSL in patients presenting with a space-occupying lesion, even with previously confirmed demyelination, and that the interval between the two events may be several years.