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Therapy-related myeloid neoplasm (t-MN) is a distinctive clinical syndrome occurring after exposure to chemotherapy or radiotherapy.  t-MN arises in most cases from a multipotential hematopoietic stem cell or, less commonly, in a lineage committed progenitor cell.  The prognosis for patients with t-MN is poor, as current forms of therapy are largely ineffective.  Cytogenetic analysis, molecular analysis and gene expression profiling analysis of t-MN has revealed that there are distinct subtypes of the disease; however, our understanding of the genetic basis of t-MN is incomplete.  Elucidating the genetic pathways and molecular networks that are perturbed in t-MNs, may facilitate the identification of therapeutic targets that can be exploited for the development of urgently-needed targeted therapies.