Allogeneic BMT offers the possibility of cure for a variety of hematopoietic malignancies, but disease relapse remains a major cause of treatment failure. This report describes two cases in which flow cytometric cell sorting (FACS) and molecular chimerism analysis were combined to increase the sensitivity of minimal residual disease (MRD) detection. In the first case this approach was used to demonstrate that a suspicious phenotype was not recurrent leukemia, thus preventing the use of potentially toxic therapy. In the second case the recurrence of a leukemia which was undetectable by conventional analysis was confirmed. The potential benefits of combining these MRD detection methods are discussed.