Succinate dehydrogenase complex iron sulfur subunit B (SDHB) is a 31.6 kDa protein coded by the SDHB gene at chromosome 1p36.1-p35. SDHB forms the succinate dehydrogenase protein complex II together with SDHA, SDHC and SDHD. Within this complex, SDHB is linked to SDHA at the catalytic end of the SDH protein complex which protrudes into the mitochondrial matrix while SDHC and SDHD are hydrophobic and attach the SDH complex to the inner mitochondrial membrane. SDH plays a pivotal role in both the citric acid cycle and the respiratory chain. It catalyzes the conversion of succinate to fumarate in the citric acid cycle downstream of IDH2.  A loss of enzyme activity results in accumulation of metabolic intermediates similarly as under hypoxic conditions. Such a “pseudohypoxia” results in HIF-1 pathway activation and may induce a metabolic shift toward aerobic glycolysis. SDHB germline mutations can cause pheochromocytoma, paraganglioma, gastrointestinal stromal tumor (GIST), and renal cell carcinoma. Paragangliomas with SDHB mutations are often malignant. SDHB immunohistochemistry is a surrogate tool for assessing the entire SDH complex (SDHA, SDHB, SDHC, SDHD) including the activity of its assembling factor SDHAF2. If any of these components is lost, the entire SDH complex either becomes unstable or does not form. As a result SDHB is released into the cytoplasm where it degrades rapidly. This loss of expression of SDHB can be detected by IHC.