Limited immune responses to tumor-associated carbohydrate antigens (TACA) are due in part to their being self-antigens. Immunization with xenoantigens of TACA provides an approach to break tolerance and augment responses to TACA. Carbohydrate mimetic peptides (CMPs) as xenoantigens can induce serum antibodies that target shared carbohydrate residues on differing carbohydrate structures. In preclinical studies, we observe that CMP immunization in mice induce immune responses that are effective in inhibiting the in vitro and in vivo growth of breast cancer and melanoma tumor cells expressing self-target antigens. CMPs of TACA can be further defined that induce IgM antibodies with broadened responses to both breast and melanoma cells. Consequently, CMPs are effective at generating a multifaceted carbohydrate-reactive immune response that should be clinically evaluated for their ability to amplify carbohydrate immune responses against circulating or disseminated tumor cells.