Correct diagnosis of acute promyelocytic leukemia (APL) requires proof of the translocation (15;17)(q24;q11), which appears to be absolutely specific for this particular type of myeloid disorder. We studied the karyotypes of 29 consecutive APL patients at diagnosis: in 5 of them banding techniques failed to detect the t(15;17). In these seemingly cytogenetically negative cases, fluorescence in situ hybridization (FISH) with a chromosome 17 painting probe detected a high percentage of mitoses with 3 hybridization signals: one derived from the intact chromosome 17, and 2 from the rearranged chromosomes 15 and 17. Trisomy 8 (+8) as a secondary chromosomal abnormality was observed in 8 cases (27.5%), confirming that the t(15;17) favors the acquisition of an extra chromosome 8. One of these 8 cases showed a marker that was interpreted by FISH analysis as der(8) with duplication of a segment of the long arm carrying the c-MYC allele. Clinical features of patients with t(15;17) and +8 were no different from patients with t(15;17) alone. The usefulness of FISH to standard banding techniques in the detection of specific structural and/or numerical chromosomal abnormalities is confirmed in this report.