The distinction of HS with BM involvement from acute myeloid leukemia (AML) with monocytic differentiation is difficult and depends on integration of morphology (large, usually pleomorphic cells > 20 μm in diameter with abundant cytoplasm [18]) and phenotypic characteristics, particularly the absence of the myeloid markers CD33 and myeloperoxidase and positivity for at least one histiocytic marker (i.e., either CD4, CD11c, CD14, CD68, CD163, or lysozyme), considered as a prerequisite for the diagnosis of HS, as shown in case 1. This evidence concerns the gene ITGAX and histiocytic sarcoma.