Chemotherapy is an essential component of therapy for infants and children with hepatoblastoma. Vincristine has been a mainstay of chemotherapeutic regimens used by North American cooperative groups, based on indirect evidence of benefit and an assumption of minimal added toxicity. European cooperative group trials have reported comparable survival rates using regimens that omit vincristine. Further examination of the risk and benefit profile of vincristine relevant to hepatoblastoma clinical care paradigms is thus warranted. We evaluated the incidence of vincristine-related sensorimotor peripheral, autonomic, and cranial nerve neurological morbidities in 45 consecutive hepatoblastoma patients treated at our institution. Data suggest an increased risk of vincristine-associated neuropathic grade 2 and 3 events (neuropathic pain and gross motor impairment) in children ages 24 months old or younger, and particularly in children born prematurely. Formal prospective investigation of the relative risks and benefits of vincristine in hepatoblastoma treatment is warranted to assess the value of continued use of vincristine in this patient population.