To investigate the peculiar regulatory mechanism of miR-219-5p on the development of melanoma, we retrieved two important databases, TargetScan 7.0 and miRanda, and found Bcl-2 may be an important downstream targeting gene, and we confirmed that the Bcl-2 protein level was significantly inversely correlated with the miR-219-5p level in tumor tissues. The gene discussed is BCL2; the disease is neoplasm.