The automated BioView Duet system was compared with manual technologist scoring (MTS) using a BCR/ABL dual-fusion FISH (D-FISH) probe strategy for chronic myeloid leukemia (CML) specimens. In the first study, 500 nuclei were evaluated for 10 distinct signal patterns in various abnormal cell percentages from each of 89 specimens. The Duet system correctly identified all 27 normal specimens and the abnormal signal pattern of all 63 abnormal specimens. The percentage of abnormal nuclei detected was also concordant, with an average difference between MTS and the Duet system of only 2.7%. However, achievement of accurate quantitative results required reclassification by a technologist for nearly 50% of nuclei per specimen. Next, the Duet system was used to evaluate BCR/ABL D-FISH for FISH minimal residual disease (MRD) detection in CML patients. Up to 6,000 nuclei were evaluated for four signal pattern categories for each of 60 CML MRD samples. Excluding four abnormal specimens with insufficient samples, the Duet system correctly identified all of the abnormal specimens and identified four additional abnormal specimens previously diagnosed as normal by MTS. The technologist time required for evaluation and reclassification of the Duet system data for the FISH MRD samples averaged only 1 minute per case, saving significant technologist effort. We conclude that the Duet system appears to be more sensitive and cost-effective than MTS for CML FISH MRD testing.