SDH-deficient GISTs, characterized by negativity at SDHB immunostaining, constitute the largest pathogenetically characterized subgroup among cases WT for KIT and PDGFRA. Their pathogenesis basically follows the classic tumor-suppressor gene model, with both alleles of one of the four SDH subunits inactivated in the tumor cells, either on a mutational (often with a germline component) or epigenetic (SDHC hypermethylation) base, possibly presenting in syndromic settings (Carney triad or Carney-Stratakis syndromes) [3, 12, 28, 34]. Here, SDHB is linked to Carney-Stratakis syndrome.