Tehran University of Medical Sciences International Journal of Hematology-Oncology and Stem Cell Research 2008-2207 13 2 2019 04 10 72 82 Elham Nazar Department of Pathology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran Fatemeh Khatami Chronic Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran Hiva Saffar Department of Pathology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran Seyed Mohammad Tavangar Department of Pathology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran. AND Chronic Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran 2018 10 26 2019 01 28 Transformation of a normal cell to cancerous one is dependent on the accumulation of several genetic and epigenetic alterations. One of the candidate driver genetic alterations can happen in succinate dehydrogenases (SDHx) coding gene include SDHA, SDHB, SDHC, SDHD, and SDHAF2.  The most important SDH mutation is in the SDHD gene, which encodes the smallest subunit of mitochondrial complex II (SDH). It has key function both in familial and non-familial hereditary paraganglioma/phaeochromocytoma syndrome (HPGL/PCC). SDHx genes mutations can have resulted in genetic and epigenetic changes like histone hypermethylation. These properties can lead to succinate-mediated inhibition of α-ketoglutarate-dependent dioxygenases. So hypoxic conditions can generate subsequent neoplastic transformation, and in this review, we are presenting the role of SDHx in several malignancies. https://ijhoscr.tums.ac.ir/index.php/ijhoscr/article/view/1015 https://ijhoscr.tums.ac.ir/index.php/ijhoscr/article/download/1015/782