Objective We initiated a prospective study of very young children with cancer, in comparison with matched healthy children, to investigate neurodevelopmental consequences of non-CNS cancers and treatment. Methods A total of 61 children (≤42 months) with non-CNS cancers and 61 matched controls underwent an identical age-appropriate neuropsychological test battery. Results Children with cancer manifested deficits compared to healthy controls in motor, mental, and language development, but were similar to controls in cognitive representational abilities and emotional relationships in interaction with their mothers. Better physician-rated health status at diagnosis and mother-rated behavioral status 1 month prior to assessment were associated with better motor and mental performance in the cancer group. Conclusions This study identifies deficits as well as spared functions in children with non-CNS cancers; the results suggest ways parents and healthcare professionals may plan specific remediations to enhance quality of life in young cancer survivors.