Although many experimental tumor models have demonstrated the importance of CTL, Th1 response, and NK cells in antitumor immunity, relatively little is known about the role of B cells in tumor immunity. The ability and mechanism of B cell-mediated regulation of cellular immune responses and inflammation have only recently been described and remain incompletely understood. Although B cells are recognized as a significant proportion of tumor-infiltrating lymphocytes in both mouse models and human tumors, relatively little mechanistic information is available describing how these cells influence antitumor immunity and immunosurveillance. Recently, studies in several murine models have found an association indicating that reduced number of tumor-infiltrating B cells is associated with improved CD8+ T cell and NK cell infiltration into the tumor bed and decreased tumor growth. Multiple mechanisms have been implicated in B cell-mediated suppression of antitumor immunity including (1) preferential polarization of immune responses to Th2; (2) direct suppression of tumor immunity by immunosuppressive regulatory B cells (Breg), and (3) coordination of regulatory T cell (Treg) recruitment and suppression within the tumor microenvironment. Because B cells are readily targeted in the clinic with monoclonal antibodies, understanding of how these cells influence tumor immunity may lead to rapidly translatable approaches to enhancing therapeutic immunity for both solid and hematological malignancy.