Many of the acquired genetic changes that contribute to the molecular pathogenesis of leukemia are well characterized. The relative simplicity of the tumor genetics of the common subtypes of leukemia and the availability of archived material in the form of archived neonatal blood spots (ANB or Guthrie cards) has permitted the tracing of many genetic events to fetal origins using sensitive amplification methods. We here described methods for cloning translocations and other rearrangements for “backtracking” studies, and methods for sensitive detection of such rearrangements and a point mutation in ANB cards.