SDH‐deficient RCC shows uniform absence of SDHB reactivity on IHC, owing to a biallelic inactivation of any of the four SDH genes (primarily SDHB, and much less frequently SDHA, SHDC, or very rarely SDHD), which are almost always associated with germline mutations and a somatic second hit (Figure 4E).64, 70, 71, 72, 73, 74, 75, 80. The gene discussed is SDHB; the disease is renal cell carcinoma.