It is well known in the literature that cancer creates educationally related barriers for all children, which may or may not contribute to clinically relevant school problems. The goal of this study was to obtain a base rate for the characteristic pattern of school functioning for children with leukemia, so that the children with the most serious difficulties might be discovered and given the different and flexible help needed. From 1988 through 1994, a questionnaire was administered annually to teachers of all leukemic children in our center. The 291 questionnaire were used to compare the school functioning of children with leukemia with that of matched controls chosen by each teacher as representative of the class as a whole, excluding special education and developmentally disabled students. This approach to matching was chosen as a control for socioeconomic factors as well. The study was conducted with all patients with leukemia entering the center residing in the region of Lombardy, attending school, and either in therapy or out of therapy. After initial treatment, the children with leukemia in our center as a group attended school regularly and willingly. Analyses of variance (ANOVAs) were conducted on the total scores and on scores for each of the subareas of learning, socialization, and emotionality. T-tests, were given to contrast individual item scores of patients with those of their matched controls. On most individual items, children with leukemia did not differ from their classmates. However, significant discrepancies between children with leukemia and their classmates appeared consistently year after year on overall total scores and on each of the three major subcomponents of the test (learning, socialization, and emotionality). The groups most affected were children who were cranially irradiated and children who were under 6 years of age at diagnosis. Children who have been irradiated and children diagnosed under 6 years of age have the greatest risk for difficulties in school functioning and are candidates for greater attention and preventive efforts.