According to molecular features, ESCC can be classified into three different subtypes: ESCC1, with somatic alterations similar to other SCCs, some of them associated with poor prognosis and resistance to chemo-radiotherapy; ESCC2, with a greater leukocyte infiltration and a higher expression of the bone marrow stromal antigen 2 (BST2) immunomodulatory molecule; and the ESCC3 characterized by alterations predicted to activate the Phosphoinositide 3-kinases (PI3K) pathway and aspects as non-identifiable in other SCCs. Here, BST2 is linked to esophageal squamous cell carcinoma.