In this article, we present a review of data from the literature concerning the deregulation of the expression of S100A8 and S100A9 in acute myeloid and lymphoid leukemia (AML and ALL, respectively), along with an analysis of their impacts on the proliferation and apoptosis of leukemic cells that integrates the action of both proteins on the hematopoietic microenvironment. This evidence concerns the gene S100A8 and acute myeloid leukemia.