Macrophage inhibitory cytokine-1 (MIC-1) is a divergent member of the TGF-beta superfamily. Although it has been reported to exhibit both tumorigenic and antitumorigenic activities, Boyle et al. report in this issue that MIC-1 expression was correlated with the tumorigenicity of melanoma cells. The elucidation of signaling pathways around MIC-1 might contribute to prospective targeting therapy for melanoma.