Only properly mature dendritic cells (DCs) in the presence of tumor antigens accomplish to activate all of the elements of the immune network and have the potential to induce tumor-specific effectors and memory T cells. In the current study, we firstly aimed to investigate the in vivo maturation of antigen presenting cells (APCs) at the molecular level by following the expression of CD11c, CD86 and MyD88 genes in the mixture of mononuclear cells after treatment of mice with a tumor vaccine composed of C-class CpG oligodeoxynucletides (CpG ODN) and irradiated melanoma B16F1 tumor cells. The second objective was to define whether the tumor vaccine induces generation of memory T cells (CD44hiCD62Llo/hiCD27hi). Finally, based on gene expression pattern we aimed to determine the tissue distribution and homing of the (mature) APCs and memory cells after vaccination. We demonstrated that by tumor vaccine the APCs (including DCs) are manipulated in vivo. By this kind of vaccine, the differentiation and maturation of APCs is triggered primarily in the spleen and is subsequently followed by the migration of these APCs to the bone marrow. Once in the bone marrow, these APCs play a crucial role in the development and maintenance of long-lived memory T cells capable of preventing a relapse of malignant disease. In conclusion, our results provide insight into the nature and scope of the antitumor immune response elicited by this kind of tumor vaccine in vivo. We showed that the maturation of APCs is a prerequisite for the generation of effective long-term antitumor immunity.