BACKGROUND According to the World Health Organization (WHO), recurrent cytogenetic abnormalities define many specific groups of hematopoietic tumors of acute myeloid and lymphoblastic leukemia, and these abnormalities are often strongly associated with prognosis and sometimes require specific treatments. These rearrangements are commonly detected by conventional and molecular cytogenetic techniques. OBJECTIVE Using an alternative method, we sought to highlight the presence of chromosomal rearrangements. METHODS We applied molecular combing to detect and directly visualize gene fusions associated with balanced translocations found in acute leukemia. RESULTS In patients harboring t(12;21)(p13;q22), we demonstrated the presence of the fusion using specific probes covering the ETV6 and RUNX1 genes, with a positive result occurring due to the hybridization of the two probes to the same DNA fiber. Thanks to molecular combing, we also showed the presence of different breakpoints using these same probes. CONCLUSIONS Using several probes that are specific to the most common genes involved in acute leukemia, molecular combing could be an interesting additional tool in acute leukemia diagnosis.