The molecular basis of acute lymphoblastic leukemia (ALL) of both B-cell and T-cell lineages seems better understood using polymerase chain reaction (PCR) methods. The analysis of clone-specific junctional regions of rearranged genes for both Immunoglobulin (Ig H) and T-cell receptor (TcR) is the most sensitive tool for detection of minimal residual disease (MRD) in ALL. Because of the heterogeneity of all ALL patients examined in several studies, the detection of MRD at different times of treatment has not as yet been correlated with disease outcome. In contrast, T-ALL is a homogeneous disease characterized by expansion of a single clone showing a specific Rearranged junctional region of TcR delta and/or gamma genes. The use of a clone-specific probe allows detection of residual leukemia throughout treatment. However, 60 % of patients with T-ALL relapse during treatment or towards the end of therapy, with resurgence of the original leukemic clone. It is possible that the detection of MRD at a specific time-point after diagnosis, as well as at the beginning of maintenance, may help to identify a group of T-ALL patients at high risk of relapse. The correlation between detection of MRD and treatment phase may be used in the future to evaluate whether treatment regimens can be improved allowing for stratification, based on PCR-mediated detection of MRD.