Cell apoptosis plays a critical role in initiation and progression of tumor and autoimmune diseases, resistance and susceptibility to various therapeutic agents. Our previous study showed that metabotropic glutamate receptor?3 (Grm3) may be involved in autoreactive B-cell apoptosis in a B-cell-depleted agent atacicept-treated lupus-like mice. In the present study, we explore whether Grm3 is involved in the apoptosis in B-cell-related tumor including multiple myeloma and B-cell leukemia. We found that human B-cell leukemia cell line Nalm-6 cells and mouse myeloma cell line SP 2/0 cells could express Grm3. In addition, Grm3 expression emerged mainly in the middle stage of Nalm-6 and SP 2/0 cell apoptosis. Furthermore, apoptosis-induced agents effectively upregulated Grm3 expression in SP 2/0 cells. Critically, Grm3 deficiency promoted tumor progression in an SP 2/0 xenograft mouse model by suppressing cell apoptosis, whereas Grm3 overexpression effectively upregulates SP 2/0 cell apoptosis. Finally, we showed that Grm3 mediated cell apoptosis by Foxo1. Together, our data suggest that Grm3 effectively suppresses the mouse myeloma cell line SP 2/0 cell growth by mediating apoptosis. Thus, Grm3 may be used as an indicator in apoptosis of B-cell-related tumor and a potential target for the treatment of B-cell-related tumor including multiple myeloma and B-cell leukemia.