The melanoma differentiation-associated gene-7 (MDA-7) was isolated while screening for upregulated genes in terminally differentiated melanoma cell lines. Preclinical studies attempted to test the theory that oncogenesis arises from a cellular differentiation process culminating in dysregulation of the cell cycle and ultimately malignancy. The MDA-7 gene (gene symbol IL-24) has been classified as part of the IL-10 family of cytokines demonstrating significant anticancer potential. Preclinical studies have shown that MDA-7/IL-24 is effective in inducing cancer cell death by several pathways in various tumor models. A Phase I clinical trial studying intratumoral injections of solid tumors showed evidence of clinical activity with limited toxicity. This small trial suggested therapeutic potential. Results are reviewed. Future opportunities involve combination with different gene delivery systems with systemic potential.