Human cancers carry hundreds of non-synonymous mutations, several dozens among which may lead to the generation of tumor-specific MHC Class I-restricted epitopes. Hence every patient's tumor harbors a highly specific mutational and antigenic signature and up to 95% of these mutations are unique. This "mutanome" can be identified by deep sequencing and can be subjected to systematic analyses of the immunogenicity of mutated proteins/peptides. We anticipate that this approach will lead to individualized immunotherapies by means of tailored vaccines.