Background: IVLBCL is potentially treatable but difficult to diagnose. Methods: A case of progressive leg weakness and sphincter dysfunction diagnosed only at autopsy. Results: A 72 year old female presented with three weeks of increasing leg weakness and three days of urine and stool incontinence. Electrophysiological testing showed reduced tibial and peroneal CMAPs, preserved sural SNAPs, and bilateral gastrocnemius fibrillations, consistent with a pre-ganglionic lesion. Lumbosacral MRI with gadolinium showed no abnormalities. CSF was examined three times (protein 1.18-1.25, glucose 2.6-3.1, normal cell count and cytology). Whole-body FDG PET scanning showed hypermetabolic foci at the tongue base and in the mediastinum, but biopsy of both revealed no abnormality. Leg weakness progressed over three months and spread to the arms despite a course of IVIg. Four months later she died of cardiorespiratory arrest. Autopsy revealed the presence of large atypical B-cells within the lumen of small and medium sized vessels in numerous organs. There was evidence of anterior spinal artery obstruction with lymphocytes and anterior horn infarction in the lumbar cord. Conclusions: Although the literature reports that IVLBCL responds well to chemotherapy, this patient illustrates the difficulty of ante-mortem diagnosis. Nerve root biopsy may be warranted in such patients.