MicroRNAs (miRNAs) are small non-coding RNAs with post-transcriptional regulatory functions. Their role in normal hematopoiesis is being elucidated by an increasing number of studies, revealing specific variations of the miRNome (defined as the full complement of miRNAs in a genome) during the commitment and development of the hematological stem cells in the different lineages. Aberrancies of the normal miRNome have also been well documented in almost all hematological malignancies, suggesting, in most cases, specific miRNA-signatures. Intriguingly, some of the miRNA-expression abnormalities described in leukemias and lymphomas can be interpreted on the basis of the miRNome variations during normal hematologic ontogeny, revealing their origin from the particular differentiation stage in which the hematopoietic differentiation has been ‘frozen’ in the malignancy.