Malignant melanoma is a lethal form of skin cancer and highly metastatic tumor with poor prognosis; BEL β-trefoil, a lectin, obtained by our group, possesses the ability to act specifically on malignant cells. Therefore, the aim of our study was to investigate the effects of BEL β-trefoil in melanoma cells in an attempt to evaluate its potential usage as anticancer agent. BEL β-trefoil was purified by chromatography and A375 and MeWo melanoma cells were treated. Viability and proliferation were evaluated as well as apoptosis, RUNX2 gene expression and migration ability. The treated tumor cells decreased viability as well as proliferative ability. Flow cytometry analysis showed a lessen effect of the treatment on apoptosis. The gene expression analysis showed a reduction of RUNX2 expression in a dose-dependent manner and migration ability was reduced significantly in both treated cell lines. Our findings suggest that BEL β-trefoil can be considered a useful tool against malignancy due to its effect based on the simultaneous proliferation ability reduction as well as the inhibition of migration capacity on melanoma tumor cells.