Epitopes of MUC1 have been found that are recognized and required by the different MUC1 specific T cell populations (CD4 and CD8) mediating antitumor responses. Vaccination with peptides derived from the amino acid sequence of MUC1 cytoplasmic tail generated protective immune responses against MUC1-expressing tumors in MUC1 transgenic mice. Survival of MUC1 transgenic mice challenged with MUC1-expressing B16 or Panc02 tumor cells was significantly prolonged following vaccination with three overlapping peptides spanning the entire cytoplasmic tail portion of MUC1. Further, vaccination with MUC1 cytoplasmic tail peptides did not induce detectable autoimmune responses. These results demonstrate the importance of immunogenic epitopes outside of the tandem repeat of MUC1 and indicate that immunization with MUC1 cytoplasmic tail peptides is an effective anti-cancer immunotherapeutic approach.