When expressed in post-natal hematopoietic cells under the control of Mx1-Cre, Nras G12D/+ leads to either histiocytic sarcoma or a chronic MPD resembling CMML in 50% of mice, whereas Nras G12D/G12D leads to acute MPD with the expansion of myeloid compartments in all mice. Here, NRAS is linked to histiocytic sarcoma.