AIM: Although Bacillus Calmette-Guérin (BCG) vaccine is known to be effective at reducing the incidence of melanoma tumours, its efficacy has been shown to be variable. Our studies aimed at exploring the use of unloaded gelatin nanoparticles as an alternative therapy in melanoma treatment. METHODS. An enzyme-linked immunosorbent assay was used to compare the in vitro fibronectin-binding properties of BCG vaccine, PS1 (a glucan extracted from Tice® BCG), aqueous gelatin solutions, and gelatin nanoparticles. The ability of these agents to suppress murine B16-F0 melanoma in vivo was also investigated. RESULTS. Gelatin nanoparticles and aqueous gelatin solutions both exhibited a significantly stronger net binding to fibronectin in vitro than BCG vaccine. The immunostimulant PS1 did not bind fibronectin. In vivo, PS1 and aqueous gelatin were ineffective at preventing melanoma growth. However, BCG vaccine and gelatin nanoparticles both suppressed melanoma tumour formation, with the nanoparticles exhibiting significantly greater activity. CONCLUSIONS. The ability of BCG vaccine to inhibit melanoma growth is not related to the presence of immunostimulatory cell surface glucans but may possibly be attributed to its fibronectin-binding properties. Aqueous gelatin solutions were ineffective at preventing melanoma tumour formation while gelatin nanoparticles were extremely effective. This is indicative of the possibility that particulate fibronectin-binding entities might inhibit melanoma tumour formation by preventing tumour cell surface integrin binding to fibronectin in the extracellular matrix.