To determine the effectiveness of different methods for the detection of tumor cell contamination of collected peripheral stem cells, we performed a study on 39 chronic myelogenous leukemia (CML) patients who were consecutively treated at our department. Analyses of tumor cell contamination by fluorescence in situ hybridization (FISH), conventional cytogenetics, and polymerase chain reaction (PCR) showed marked differences in the percentage of evaluable results: Quantitative analysis of tumor cell contamination was feasible in 60 of 105 (57%) samples evaluated with the use of conventional cytogenetic analysis and in 105 of 107 (98%) samples analyzed by FISH. PCR was evaluable in all 85 samples tested (100%). Both methods were shown to be adequate overall in determining the number of BCR-ABL positive cells, although cytogenetics tended to produce slightly higher percentages. Based on these results, we conclude that FISH performed on leukapheresis products is a rapid and reliable method for assessing the quality of these products and should be used for routine evaluation of tumor cell contamination of CML stem cell products.