The current diagnosis of CHIP harboring a ZRSR2 pathogenetic mutation can lead to two different clinical scenarios: (i) the association between CHIP and the occasional finding of dysplastic bone marrow may represent an early detection of a subsequent MDS, or (ii) the typical clinical presentation of mastocytosis/MCAS and the finding of CD25+ spindle-shaped mast cells in the bone marrow may represent an early detection of a subsequent overt mastocytosis/MCAS predisposed by a CHIP ZRSR2-mutated clone. The gene discussed is ZRSR2; the disease is myelodysplastic syndrome.