Myxoma virus (MYXV) is a member of the Poxviridae family and the genus Leporipoxvirus. In nature MYXV tropism is restricted to lagomorphs, and is specifically pathogenic only for European rabbits (Oryctolagus cuniculus), in which this virus causes the lethal systemic disease called myxomatosis. Importantly, although MYXV cannot cause any disease pathology in humans, mice, or any other domestic animals other than rabbit, this virus can productively infect and kill a variety of human and murine cancer cells, from either primary sources or cultured cancer cell lines. Therefore, in the last decade, MYXV has emerged as a novel oncolytic virus against hematologic malignancies and various solid cancers. One novel aspect of MYXV virotherapy is a new systemic virus delivery strategy to cancer sites in the recipient, by which adsorption of the virus to isolated leukocytes is conducted prior to reinfusion of the virus-infected cells back into the recipient, via a procedure called ex vivo virotherapy (EVV, or simply EV2). The EV2 delivery strategy thus exploits the inherent migratory properties of leukocytes to ferry MYXV to tissue sites bearing cancer cells that are accessible to leukocyte chemotaxis. Here, we describe EV2 procedures with MYXV to systemically deliver the virus to sites of disseminated and/or metastatic cancer in situ via infected leukocytes derived from either bone marrow or peripheral blood.