CD37 is a cell surface glycoprotein belonging to the tetraspanin superfamily, predominantly expressed on mature B cells and at lower levels in other healthy hematopoietic cells. It interacts with various adhesion molecules, growth and signal transduction receptors, and other tetraspanins, playing a role in membrane organization, signal transduction, survival, and apoptosis. CD37 is expressed in B-cell non-Hodgkin lymphoma (B-NHL), but not all B-cell malignancies express CD37, such as 60% of follicular lymphomas (FL) and 40% of diffuse large B-cell lymphomas (DLBCL). Additionally, CD37 is detected at high levels in T-cell lymphomas and acute myeloid leukemia (AML). Functionally, CD37 plays a role in pro-survival and pro-apoptotic signaling through the PI3K/AKT pathway and controls IL-6 receptor signaling via interaction with SOCS3. It can also mediate the clustering of α4β1 integrin, activating PI3K/AKT signaling and cell survival, but at the same time, it can form complexes with SHP1, LYN, SYK, and PI3Kγ, leading to AKT inactivation and recruitment of SOCS3, limiting the IL6/STAT3 loop.