In these multi-mutated SM patients, the exact sequence of acquisition of genetic mutations remains unclear; thus, in some patients, the KIT D816V appears to be the first acquired mutation [13], while another subgroup of SM cases carries the KIT D816V mutation and mutations in genes other than KIT in different cell clones [13,36,85], and in a third subgroup of SM patients, the KIT mutation appears to be a secondary event. The gene discussed is KIT; the disease is systemic mastocytosis.