Reversible posterior leukoencephalopathy syndrome (RPLS) is a rare complication of cancer chemotherapy. We have recently observed two cases occurred simultaneously in children receiving different chemotherapy regimens, for hepatoblastoma and acute lymphoblastic leukaemia, respectively. Both children presented with altered mental status, severe visual disturbances, headache, seizures, backpain and hypertension. Magnetic resonance imaging showed cortical and subcortical lesions especially in the occipital and parietal regions, strongly consistent with RPLS. Both patients completely recovered from their neuropsychologic deficits in about ten days only with anticonvulsant and antihypertensive therapy, and chemotherapy regimen was promptly restarted according to the planned protocol, without any neuropsychological sequela. A mild left midriasis was the only neurologic defect that persisted in the patient with acute lymphoblastic leukemia.