Efficacy of novel cancer immunization protocols could be tested in cell line-derived xenograft tumor models (CDX), which are based on the implantation of human tumor cell lines into mice for the development of different tumors by numerous means, such as subcutaneous implantation and orthotopic, venial, or peritoneal injections. However, the disadvantages of this model are the biological alteration of the derived cells or the inability of the cell lines to accurately reflect the complexity of tumor heterogeneity. Therefore, syngeneic mouse models, which offer a relatively simple grafting technique, preservation of lineage hierarchy, and the ability to generate tumors in as little as 2-8 weeks, are being used to study potential future applications in medical treatment, particularly immunotherapies. Here, we describe a B16.F10 C57Bl/6 mouse melanoma model we selected for therapeutic studies employing IL-2 and IL-12 immunization protocols. Procedure of tumor cells inoculation and melanoma development in mice is described in detail, as first and necessary set-up for successful immunization experiments.