Common peroneal neuropathy (CPN) may develop unexpectedly in patients with underlying cancer. To clarify the underlying pathophysiology, clinical and neurophysiological data were prospectively collected from 10 oncology clinic patients referred for neurological assessment after the onset of foot weakness. In all patients, the CPN occurred in the setting of advanced systemic malignancy frequently associated with marked weight loss at the time of foot weakness. Neurophysiological studies localised the CPN to the fibular head in 80% of cases. Findings from this study, combined with recent experimental evidence, support the hypothesis that clinically evident CPN develops after rapid weight loss, perhaps reflecting a relative metabolic deficiency within the nerve, which exposes anatomical susceptibility and possible subclinical pre-existing nerve injury.