The development of effective immunotherapeutic approaches against cancer has been a major focus of research in the last 10–15 years. Despite the impressive progress in the last 10 years, which has incorporated purified proteins, DNA and targeting to dendritic cells and/or the use of Toll-like receptor ligands, there are still many hurdles to overcome in order to elicit effective immune responses that could totally eradicate cancer cells. MUC1 has attracted interest as a target for immunotherapy of malignancies, including solid cancers, such as breast, pancreas and ovary, and blood cancers, including multiple myeloma. Numerous methods have been shown to elicit humoral, cellular and tumor protective responses in preclinical settings. Many of these have entered into human clinical trials, which aim to evaluate the immunogenicity of MUC1 and its suitability for use in immunotherapy/vaccine for many malignancies.