Abstract: Anaplastic lymphoma kinase (ALK) gene fusions occur in a variety of tumors and have become important therapeutic targets for multiple cancer types. ALK inhibitors have demonstrated antitumor activity in various tumors with ALK gene fusion. However, the presence of ALK gene fusions and the therapeutic response to ALK inhibitors in melanoma remain unclear. This article reports a case of a patient with acral melanoma harboring a ALK gene fusion, who initially received adjuvant pembrolizumab therapy followed by combination treatment with temozolomide plus apatinib and pembrolizumab, but experienced disease progression. Subsequent treatment with lorlatinib resulted in significant tumor shrinkage. This case suggests that ALK inhibitors may serve as a therapeutic option for patients with melanoma harboring a ALK gene fusion.