Recurrent hot spot mutations Y640F and D661Y/V/H/N in the SH2 domain of STAT3 have been identified most commonly in T-LGL leukemia, NK, NK/T, and adult T cell leukemia/lymphoma (ATLL) patients, while the aggressive STAT5BN642H mutation has been predominantly found in T-ALL and γδ-T cell lymphomas, such as hepatosplenic TCL, monomorphic epitheliotropic intestinal TCL, and primary CTCL (Figure 2) [113]. Here, STAT3 is linked to primary cutaneous T-cell non-Hodgkin lymphoma.