Bone marrow failure syndromes are disorders of hematopoietic stem cell that can lead to peripheral pancytopenia and marrow hypoplasia, also called aplastic anemia (AA). AA can be inherited or acquired. The main causes of inherited AA are congenital in nature, as it is in Fanconi anemia (FA). FA is mostly an autosomal recessive disorder, with familial aplastic anemia, chromosomal breaks, different congenital anomalies and increased cancer susceptibility. Nature of cause and therapy management is the main terms that distinguish FA from acquired AA. Specific clastogenic effect of DNA cross-linking agents, such as diepoxybutane (DEB) on FA cells and its sensitivity to it, was used for screening of FA among AA patients. Since February 2004 until February 2006, 21 children with AA and other bone marrow failure syndromes were diagnosed and treated at the Mother and Child Health Care Institute of Serbia "Dr Vukan Cupic" in Belgrade. Chromosome instability study was performed on control (DEB-untreated) and DEB-treated 72 hours cultures of peripheral blood. After 48 hours of culturing, DEB (0.1μg/ml) was added and metaphases were examined for chromosome breakage and abnormalities. In examined group of 21 patients, five of them (23.8%) were found to have increased DEB-induced chromosome breaks. The ranges of DEB-induced chromosome breaks were: for DEB-insensitive patients 0.00-0.20 and for DEB-sensitive patients 0.58-2.15 break per cell. No overlap between DEB-sensitive and DEB-insensitive group was found. The ranges of spontaneous breaks for DEB-insensitive and DEB-sensitive patients were overlapping: 0.00-0.07 and 0.00-0.27 breaks per cell respectively. Authors will discuss the significance of DEB test in differential diagnosis of AA.