SETMAR, also known as Metnase, has previously been shown to suppress the formation of chromosomal translocation in mouse fibroblasts. Despite the fact that hematological malignancies are often characterized by chromosomal rearrangements no studies have hitherto investigated the expression pattern of the gene in these disorders. We hypothesized that a high expression of SETMAR protected the cells from chromosomal rearrangements,; thus, we examined the mRNA expression of SERTMAR transcript variants in hematological patients. We identified six transcript variants (var1, var2, var5, varA, varB, varC), of which three have not been reported previously. Expression levels were quantified by transcript-specific quantitative PCR in 15 healthy individuals, 70 acute myeloid leukemia (AML) patients (translocation positive, n=30 (AMLTPos), translocation negative, n=40 (AMLTNeg)), seven patients with mantle cell lymphoma (t(11;14) positive), and 13 patients with chronic myeloid leukemia (t(9;22) positive). All variants were significantly overexpressed in both subgroups of AML compared to healthy individuals (var1and var2: p<0.00001 for both AML subgroups, varA and varB: p=0.0002, var5: p=0.0008 and varC: p=0.0001 for AMLTNeg. varA: p=0.0048, varB and var5: p=0.0001, varC: p=0.0017). When comparing the expression in AMLTNeg and AMLTPos we found a significant increased expression of the full length SETMAR in AMLTNeg (var1: p=0.047), suggesting a protective effect of high SETMAR expression on formation of chromosomal translocations. Conclusively, we have identified known and novel SETMAR splice variant to be significant increased in AML, This is, to our knowledge, the first study that describes an expression profile of SETMAR in subgroups of hematological malignancies, which can be linked to the incidence of chromosomal rearrangements.