B-cell lymphoma 2-related protein A1 (BCL2A1) is a member of the BCL-2 family of anti-apoptotic proteins that confers resistance to treatment with anti-cancer drugs. Immunohistochemical expression of Wnt11 and BCL2A1 in complete moles and normal villi. Bcl2 family proteins control mitochondrial apoptosis and its members exert critical cell type and differentiation stage-specific functions, acting as barriers against autoimmunity or transformation. Anti-apoptotic Bcl2a1/Bfl1/A1 is frequently deregulated in different types of blood cancers in humans but its physiological role is poorly understood as quadruplication of the Bcl2a1 gene locus in mice hampers conventional gene targeting strategies. In a physiological context, BCL2A1 is mainly expressed in the hematopoietic system, where it facilitates survival of selected leukocytes subsets and inflammation. However, BCL2A1 is overexpressed in a variety of cancer cells, including hematological malignancies and solid tumors, and may contribute to tumor progression. The development of small molecule inhibitors of BCL2A1 may be a promising approach mainly to sensitize tumor cells for apoptosis and thus improve the efficiency of anti-cancer therapy.