Background: A 28 year old male with a previous diagnosis of Ewing’s Sarcoma in 2008, and a revised diagnosis to Hodgkin’s lymphoma in 2016, presented to the Neurology service 6 months after starting the novel monoclonal antibody, Brentuximab. Concurrent therapy included adriamycin, vincristine and daunorubicin. He was referred for progressive weakness and sensory symptoms starting in the legs and spreading to the arms over 6 months. Methods: Examination demonstrated distal symmetric weakness with power of 3 proximally and distally in the lower extremities. Reflexes were absent at the ankles and severely reduced at the patella. Gait was consistent with a sensory ataxia, and there was pseudoathetosis of the left hand. Results: MRI demonstrated no relevant abnormalities. Electrophysiology was consistent with a motor predominant, distal symmetric sensorimotor axonal neuropathy. Conclusions: A review of the literature demonstrated that the monoclonal antibody brentuximab has a high incidence (48%; n = 89) of a reversible distal symmetric polyneuropathy. The mechanism likely relates to microtubule dysfunction by the conjugated compound monomethyl auristatin E. This case adds to the existing body of literature around a severe but potentially reversible neuropathy, resulting from the new monoclonal antibody brentuximab, which may also serve as a model of disease in neuropathy with a well elucidated mechanism of toxicity.