Synthetic antigen-encoding mRNA is increasingly exploited as a tool for delivery of genetic information of complete antigens into professional antigen presenting dendritic cells for HLA haplotype-independent antigen-specific vaccination against cancer. Two strategies for mRNA-based antitumor vaccination have emerged into the clinical setting. One is transfection of autologous dendritic cells with synthetic mRNA for adoptive transfer into the patient. The other is direct injection of naked synthetic mRNA. Both methods have proven to be feasible and safe and to elicit antigen-specific immune responses. The design of novel synthetic vaccines employing synthetic mRNA requires further in-depth investigation of its bioavailability and immune pharmacology. This chapter summarizes the state-of-art in this field and describes methods elementary for preclinical studies of mRNA-based antitumor vaccine protocols.