The link between drug resistance and relapse was often suggested, but rarely demonstrated in long-range clinical studies. Since it is nowadays recommended to validate immunocytochemical results, the authors studied prospectively 52 acute lymphoblastic leukemia (ALL) patients with an immunocytochemical test and a functional flow cytometric test. The 4-year EFS and OS were 79.3% and 85.2%, respectively. Patients scoring positive in both tests had a significantly higher relapse rate and worse survival (log rank p = 0.007 and 0.047 for event-free survival and overall survival, respectively). Among the different prognostic variables evaluated, only the combination of P-gp expression and activity was a statistically significant parameter predicting relapse in childhood ALL.