Mainly known for its cardioprotective properties, protein kinase C isoformε (PKCε) is also progressively coming of age in terms of its role in hematopoiesis regulation, particularly that is related to erythropoiesis, megakaryocytopoiesis, and platelet production. Data available to date show that PKCε is differentially regulated in erythrocyte and megakaryocyte progenitors, strongly suggesting an addressing role toward maturation of either lineage. This function appears to be played by either selecting progenitors or conducting maturation toward a specific fate. Inappropriate expression of PKCε in human mature platelets is discussed as a recently described example of functionalmodification that may acquire pathophysiologic relevance in major thrombotic diseases. Preliminary evidence suggests that PKCε expression may be used as a surrogate marker for thrombotic risk stratification and as a possible target for antiplatelet therapy in patients with thrombotic disorders.