Adaptor or scaffolding proteins mediate protein-protein interactions that drive the formation of protein complexes. Gab2 scaffolding protein is an intermediary molecule that links plasma membrane receptor signaling including receptor tyrosine kinases with the downstream effectors such as SHP2, p85 subunit of PI3K, PLCγ, CRK, SHC, and SHIP. Although well described in signal transduction, the role of Gab2 scaffolding protein in cancer has recently been emerging especially in leukemia, breast and ovarian cancer, and melanoma. Gab2 is essential for mediating the two major signal transduction pathways in cancer, the PI3K-AKT and ERK signaling pathways. This review focuses on the structure and function of Gab2, its regulatory proteins, emerging role in cancer, and potential as a therapeutic target.