Translocations involving the MLL gene on the chromosome 11 (11q23) are frequently observed in acute leukaemia. The detection of this genetic change has a unique significance as a result of its implication of poor prognosis. To reveal the utility of fluorescence in situ hybridization (FISH) in detecting the MLL translocation, we analysed 289 consecutive Korean patients (children and adults) with acute leukaemias using both conventional cytogenetic analysis (CC) and FISH, placing an emphasis on the result discrepancies. Twenty-two of 289 patients (7.6%) had the 11q23/MLL translocation. In nine of 22 patients (41%), only FISH detected the translocation. In eight of these 22 patients, a total of 19 follow-up examinations were performed, of which FISH detected a significant level of leukaemic cells harbouring the MLL translocation in five patients (26%) without cytogenetic evidence. In addition to the MLL translocation, FISH detected submicroscopic amplification, partial deletion of the MLL gene and trisomy 11 in 12 patients without cytogenetic evidence. In summary, up to 41% of the MLL translocations at initial work-up and 26% during follow-up were detected by FISH without cytogenetic evidence. Thus, we recommend that MLL FISH should be performed in the diagnosis and monitoring of acute leukaemias in combination with CC.