Fluorescence in situ hybridization (FISH) is a new technique that allows demonstrating of the bcr/abl gene fusion in bone marrow cells of patients with Philadelphia translocation (Ph)-positive chronic myeloid leukemia (CML). In this study, bone marrow samples of 150 patients were investigated routinely by interphase FISH, cytogenetics, and bone marrow histopathology. In 20 patients with reactive hyperplasia of the granulopoiesis and normal karyotypes, FISH revealed nonspecific bcr/abl fusion signals at a mean frequency of 2.7% of the cells examined. The cutoff level for specific fusion signals was set at three times the standard deviation (9.0%). None of the 29 cytogenetically Ph-negative patients with myeloproliferative disease other than CML had fusion signals exceeding 9%. The mean frequency of specific fusion signals in nontreated patients with CML (n = 59) was 92.7%, and 49.3% in patients with CML who received therapy (n = 42). For diagnosing Ph-positive CML, interphase FISH has been faster, more reliable, and more sensitive than cytogenetics, which was successful in 54 of 59 patients investigated at first diagnosis but only in 27 of 42 patients receiving therapy, and it failed to detect Ph-positive cells in three patients with CML. However, small percentages of less than 9.0% of cells with bcr/abl fusion signals were below the threshold of interphase FISH, thereby limiting its use for detecting minimal residual disease.