The majority of clonal hematologic syndromes, including lymphoproliferative, myeloproliferative, and myelodysplastic disorders, tend to undergo transformation. However, the frequency of transformation varies widely. For example, transformation is almost invariable in chronic myelogenous leukemia, but it is infrequent in other myeloproliferative disorders. Similarly, transformation occurs in approximately 33% of follicular lymphomas but less commonly in other lower-grade lymphomas. At a genetic level, although some secondary lesions are seen across the spectrum of transformation syndromes (such as loss of function of p53 and p15/p16), there is considerable intra- and interdisease variability, with no common denominator. This review of the literature will discuss these transformations, noting their frequency, pathologic changes observed, clinical syndromes described, underlying genetic correlates, and prognostic and therapeutic implications.