Background: Metastasis is a major problem for effective therapy of cancer. Small cysteine protease inhibitors, cystatins have been shown to be anti-metastatic for a number of different cancers. We have identified a small peptide of cystatin which exhibits anti-cancer properties for B16 melanoma cells in vitro. Methods: B16 melanoma cells were measured for growth, proliferation, migration, and apoptosis in the presence and absence of cystatin peptide. Results: The cystatin peptide reduced melanoma cell growth, proliferation, migration, and increased apoptosis in melanoma cells in culture. Conclusion: Cystatin peptide exhibits anti-cancer effects on highly metastatic B16 melanoma cells in culture.