Chromosomal rearrangements of the humanKMT2A/MLLgene are associated withde novoas well as therapy-induced infant, pediatric, and adult acute leukemias. Here, we present the data obtained from 3401 acute leukemia patients that have been analyzed between 2003 and 2022. Genomic breakpoints within theKMT2Agene and the involved translocation partner genes (TPGs) andKMT2A-partial tandem duplications (PTDs) were determined. Including the published data from the literature, a total of 107 in-frameKMT2Agene fusions have been identified so far. Further 16 rearrangements were out-of-frame fusions, 18 patients had no partner gene fused to 5’-KMT2A, two patients had a 5’-KMT2Adeletion, and oneETV6::RUNX1patient had anKMT2Ainsertion at the breakpoint. The seven most frequent TPGs and PTDs account for more than 90% of all recombinations of theKMT2A, 37 occur recurrently and 63 were identified so far only once. This study provides a comprehensive analysis of theKMT2Arecombinome in acute leukemia patients. Besides the scientific gain of information, genomic breakpoint sequences of these patients were used to monitor minimal residual disease (MRD). Thus, this work may be directly translated from the bench to the bedside of patients and meet the clinical needs to improve patient survival.