Background and Aims The myelodysplastic syndromes (MDS) are a diverse group of clonal myeloid disorders. Application of next generation sequencing (NGS) techniques has added to our understanding of their pathogenesis by identifying mutations in genes involved in many parts of DNA regulation. We hypothesise that mutational 'profiling' will be a useful adjunct in the diagnosis of MDS. Method Patients undergoing bone marrow examination for investigation of unexplained cytopenias were recruited at Sir Charles Gairdner Hospital. Somatic DNA was extracted from EDTA-anticoagulated marrow and constitutional DNA from buccal swabs. After DNA amplification using a custom primer panel genomic DNA was sequenced on an Ion Personal Genome semiconductor sequencer (Ion Torrent, Life Technologies). ResultsWe review the current understanding of the molecular pathogenesis of MDS and report NGS results from 21 of 30 patients for whom we had evaluable matched buccal and marrow specimens. A total of 28 somatic variants were identified in post-sequencing analysis. 23/28(82%) were identified in genes known to be associated with MDS, 6(26%) of which had previously been reported. Conclusion NGS can identify somatic mutations in patients with cytopenias secondary to BM dysfunction. This suggests an analytical NGS ‘pipeline’ is technically feasible and capable of demonstrating variants in BM.