Intensified treatments aimed at maximal tumor reduction are an important therapeutic option for patients affected by B-cell malignancies. The possibility of obtaining a relevant number of clinical complete remissions after these treatments prompted the application of molecular techniques for the detection of extremely low numbers of residual malignant cells. These cells can be present either in the stem cell graft or, during the follow-up, in the bone marrow of patients attaining a clinical complete remission. The most sensitive and widely used techniques for minimal residual disease (MRD) assessment are those based on the PCR method. These methods allow the detection of autologous graft contamination and the identification of patients at high risk of disease recurrence by means of post-transplant MRD monitoring. In this setting, quantitative PCR assays can evaluate the kinetics of tumor clone growth in complete remission (CR) patients showing a persistence of PCR detectable tumor cells with standard qualitative methods.