Despite the advantages and encouraging results of using FISH technology, we demonstrated the limitation of the existing FISH signal detection and analysis methods that are based on the conventional 2-D microscopic images. The 2-D projection of 3-D objects is incapable of revealing the separation of the FISH probe pair in the depth direction due to the signal spot overlapping, thus generating detection error. Although for the majority of disease cases, this kind of missed detection may not significantly impact the final diagnostic results due to the rarity of such interphase cells depicting a translocation chromosome standing vertically along the depth direction of the 2-D image plane. However, it may potentially impact detection and diagnosis of a fraction of early and subtle (e.g., heterogeneous) cases where the ratio between abnormal and normal interphase chromosome cells is relatively small. In addition, missing abnormal cells with two FISH translocation signal spots overlapped in the 2-D projection images may also reduce the accuracy in detecting residual disease and evaluating treatment efficacy. For example, to detect an early leukemia case and/or evaluate treatment efficacy of a leukemia patient, a blood specimen is typically taken from the patient and analyzed. Due to either the early status of the disease or the relatively effective treatment, the number of abnormal cells is either quite small or has been vastly diminished during treatment. Also, unlike the solid tumor, the abnormal cells are difficult to localize in the extracted blood specimen due to blood circulation.14 As a result, one can expect that the ratio of abnormal to normal cells in these cases to be quite small (i.e., one abnormal cell in every 100 or 1,000 normal cells). Hence, in the clinical practice physicians are required to examine approximately more than 2,000 cells to make a “confident” conclusion in the disease diagnosis and/or assessment of treatment efficacy. It is therefore vital to detect every abnormal cell with the FISH-probe-targeted chromosome translocation in order to discover an early relapse of the disease. The finding in this case report suggests that the 3-D visualization approach could be a useful accessory to leverage the accuracy of detecting early and/or residual disease.