The gene PRAME (preferentially expressed antigen of melanoma) was found to be expressed at high levels in a large fraction of different tumors and adult leukemias. Since PRAME is only expressed at low levels in a few normal tissues and encodes an antigen recognized by autologous cytolytic T lymphocytes, it might be a good candidate for tumor immunotherapy. In this study, quantitative reverse transcriptase polymerase chain reaction was used to measure PRAME gene expression in 50 children with newly diagnosed acute lymphoblastic leukemia (ALL). Nine patients were also analyzed in relapse. Overexpression of PRAME was found in 42% (N = 21) of the patients. In accordance with our findings in acute myeloblastic leukemia (AML) patients, the rate of disease-free survival was higher and white blood cell counts at diagnosis were lower in patients with an overexpression of PRAME. However, in our group of ALL patients these findings were not statistically significant. The levels of expression at diagnosis corresponded well with those at relapse (P = 0.017). Although overexpression of PRAME was less frequent than in children with AML (62%) our results suggest that PRAME could be a useful target for immunotherapy in some children with ALL.