Melanoma is a malignant skin cancer that displays a high rate of tumor cell migration and metastasis. This study examined how corticotropin-releasing hormone (CRH) affects the migration of melanoma cells in order to further understand the relationship between stress and tumor cell migration. The migration assay data showed that CRH treatment increased the level of B16F10 cell migration in a dose- and time-dependent manner. To determine whether the extracellular signal-regulated protein kinase 1/2 (ERK1/2) signaling pathway is involved in the upregulation of melanoma migration, cells were pretreated with an inhibitor of ERK1/2 (PD098059). The pretreatment of PD098059 blocked the increase in cell migration. Furthermore, CRH induced the phosphorylation of ERK1/2. The maximum activation of ERK1/2 by CRH was observed at 15 min. Taken together, these results suggest that CRH is an important mediator that regulates the migration of melanoma cells in the skin during stress through the ERK1/2 signaling pathway.