Human Cripto-1 is a cell membrane protein that has been shown to be overexpressed in different types of human tumors. Because Cripto-1 is expressed at low levels in normal tissues, it represents a promising candidate for therapeutic intervention in cancer. The present patent describes a novel approach to target Cripto-1 in cancer using a vaccine. Immunization with Cripto-1 modified by addition of a foreign peptide to overcome T-cell tolerance for self-proteins has the potential to generate an antibody-based immune response that ultimately will block Cripto-1 activity in cancer cells. Although targeting Cripto-1 with a vaccine in cancer patients is promising, several experimental and clinical studies need to be done to validate this approach.