Human butyrophilin subfamily 3 member A (BTN3A), also known as CD277, includes isoforms BTN3A1, BTN3A2, and BTN3A3 and is structurally associated with B7 costimulatory molecules. Each BTN3A isoform consists of an extracellular N-terminal Ig variable (V) domain and a near-membrane Ig constant (C) region connected to a single transmembrane domain. BTN3A family members have emerged as important molecules modulating the function of Vγ9Vδ2 T cells. The B30.2 intracellular domain plays an important role in this process. Only the intracellular B30.2 domain of BTN3A1 directly binds phosphorylated antigens (pAgs) through a positively charged pocket to activate Vγ9Vδ2 T cells. BTN3A1 is expressed in many tumors, such as ovarian cancer, bladder cancer, breast cancer, renal cell carcinoma and pancreatic ductal adenocarcinoma. The prognostic role of BTN3A1 in different cancers varies substantially.