Acquired aplastic anemia (AAA) is a failure of hematopoiesis characterized by pancitopenia and bone marrow aplasia. Severe aplastic anemia (SAA) is the most aggressive type of AAA and presents less than 25% cellularity in the bone marrow and very low values of at least two hematopoietic lineages. Myelodysplastic syndromes (MDS) are a heterogeneous group of disorders characterized by a hematopoietic insufficiency leading to progressive pancytopenia and a tendency to evolve to acute leukemia. Hypoplastic myelodysplastic syndrome (hMDS) presents very low bone marrow cellularity, and is clinically very similar to SAA. The differential diagnosis consider presence of morphological alterations (often present in hMDS), response to growth factors (present in hMDS stem cells and deficient in SAA) and cytogenetic abnormalities (often present in hMDS). Both diseases are candidate for bone marrow transplant, but with distinct conditioning regimen. In order to identify biomarkers that help differentiate both diseases in the absence of cytogenetic abnormalities we performed a differential display analysis (DDRT-PCR; RNAimage - GeneHunter Corp) between bone marrow samples from two patients with SAA, two patients with hMDS and a pool of three healthy donors (an effort to reduce intrinsic polymorphisms). mRNA from mononuclear cells were extracted and retro transcribed into cDNAs using three different anchorage primers. These cDNAs were amplified with the previous primer and a randomic one using a[³³P]dCTP and the amplicons were resolved in a 6% DNA sequencing gel. One hundred and twenty five cDNAs were differentially expressed and were recovered, amplified and direct sequenced. Seventy five amplicons were analyzed using BLAST program. From these, 34 were expressed only in one patient and considered polymorphisms. Fourty one cDNAs were expressed in group of patients and 32 were mapped on known genes. Some of these genes were constitutive, like ATPase class VI and fibronectin, while others were lineage-specific like LAX1 (lymphocyte transmembrane adaptor 1). Some of the genes identified are putative biomarkers as a ligand of nitric oxide synthase (CAPON), that was overexpressed in hMDS patients and MLLT10, a "mixed lymphocytic leukemia" gene homolog that was overexpressed in healthy donors.