Background and PurposeThe role of high‐resolution nerve ultrasound (HRUS) in the diagnosis of chemotherapy‐induced polyneuropathy is unclear. The present prospective longitudinal controlled study evaluates the utility of HRUS in vincristine‐induced polyneuropathy (VIPN).MethodsTwelve patients receiving vincristine and 12 healthy age‐matched controls were included. Visits before and 3 weeks, 8 weeks, and 6 months after the start of vincristine treatment included clinical examination, the total neuropathy score (TNS), nerve conduction studies (NCSs), and HRUS of the bilateral median, ulnar, radial, tibial, peroneal, and sural nerve cross‐sectional areas (CSAs).ResultsMedian TNS increased from 0 points (interquartile range [IQR] 0) to 0.5 points (IQR 1, p = .26) at Week 3 and to 4 points (IQR 2.5, p < .001) at Week 8. At 6 months, there was a nonsignificant decrease to 2 points (IQR 2, p = .66). HRUS of individual nerve sites showed no significant changes in CSA and intranerve variability. The total CSA of all entrapment sites increased significantly (p = .007) at Week 8. Sensory nerve action potentials decreased significantly after 6 months (sural nerve, p = .001; radial nerve, p = .004; ulnar and median nerve, p < .001). The tibial nerve compound muscle action potential (p = .006) and nerve conduction velocity (p < .001) were reduced.ConclusionsAt mid‐treatment, there is an increase in the total CSA at entrapment sites parallel to an increase in clinical symptoms. In individual nerve sites, HRUS does not detect significant signs of VIPN. NCSs exhibit signs of a predominantly sensory axonal polyneuropathy. The clinical examination remains the most sensitive tool in the early detection of VIPN.