Acute Promyelocytic Leukemia (APL) is characterized by the PML-RARA fusion gene, as a consequence of the t (15;17(q22;q21) translocation. Depending on the PML breakpoint, usually located within intron6, exon6, or intron 3, different PML/RARA transcript isoforms may be generated: long (bcr1), variant (bcr2), and short (bcr3), respectively. We report the characterization of a case of APL with atypical PML/RARA transcript, which was not clearly detectable using standard molecular procedure. Differential detection of PML-RARA bcr1, bcr2, bcr3 fusion transcripts were analyzed using a LAMP technology based kit (DiaSorin Molecular) and no amplification detected. Subsequently a Real time PCR performed using HemaVision-28Q kit (DNA Diagnostic), no detecting amplification. Given the strong clinical and morphological suspicion, we tested the sample for RT-PCR (Biomed protocol) using PML-A2 and RARA-B primers. Analysis of PCR product showed one specific band of 440 bp, a size that does not correspond with the recognized size of the typical transcripts. The immunophenotipic characterization carried out on FACS CANTO II BD, showed 90 % of abnormal mononuclear cells 45% of which expressed CD34 and a myeloid phenotype (positive for CD117, CD13, CD33 and partial for CD2 and MPO). Apart from this population with the help of logical gate, we found a population that did not express CD34 and HLA DR and had cytometric characteristics of APL. Analysis of the bone marrow (BM) aspirate demonstrated a markedly hypercellular marrow with 40% myeloblasts and 30% abnormal promyelocytes of medium-sized, with bilobed nuclei and hypergranulated cytoplasm and rare Auer bodies. The traditional cytogenetic analysis at the diagnosis, assayed by the R- banding, revealed the following karyotype: 46, XY, t(15;16;17) (q24;p13;q21) [18]/47, XY, +8, t(15;16;17) (q24;p13;q21)[2]. In this report, we describe a patient with this specific translocation involving three chromosomes: 15, 17 and 16