Breast cancer is the most common cause of death from cancer among women. “A proliferation-inducing ligand” (APRIL) is seen in the stroma of approximately 38% of breast cancer patients. APRIL is a tumor necrosis factor superfamily member that is implicated in lymphoid cell survival, proliferation and apoptosis. APRIL studies initially focused on lymphoid cells as known APRIL receptors are exclusive to these cells. However, I found that APRIL promotes breast cancer cell proliferation, and an APRIL-specific blocking peptide inhibits APRIL-induced proliferation. Therefore, I sought to identify APRIL targets in breast cancer cells. Among those identified, colony-stimulating factor 2 receptor beta (CSF2RB) is interesting. CSF2RB-APRIL interaction is direct, and the CSF2RB ligand, CSF2, has 41% amino acid sequence similarity to APRIL. CSF2RB-linked Akt and STAT3 signaling are activated in APRIL-mediated breast cancer cell proliferation. Thus, my findings raise the possibility that CSF2RB is a novel APRIL receptor in non-lymphoid cells.