e21536 Background: Acral lentiginous melanoma (AML) is infrequent malignant melanoma subtype (5%) .It does not have specific treatment. The objective of this article is to summarize the best available evidence regarding the specific treatment of metastatic acral lentiginous melanoma. Methods: A systematic review of the literature was proposed. A search was carried out in the databases of Pubmed, Embase, Scopus, Lilacs in English and Spanish, during the last 20 years. The equation used was ((“acral lentiginous melanoma”) AND (“Treatment”)). For quality assessment, the JAMA guidelines for qualifying and globally through the GRADE system, the Cochrane guideline for evaluation of clinical trial bias was used. The review process involved 3 researchers and differents filters for evaluating the scientific evidence. The primary outcome was overall survival (OSm) and progression-free survival (PFS) as a secondary outcome. Results: 208 articles were found, only 3 articles were included. No phase 3 clinical trial. The summary of the data and qualification of evidence are in Table. In total there were 63 patients. It was found high heterogeneity in the 3 studies. The outcomes were those reported directly from each study, a subgroup analysis was not required. In first study, overall survival 21.1m was found with Dasatinib and PFS 2.8m. The second clinical trial, found OS with Nivolumab of 28.7% at 3 years. The last study was observational, and included three different treatment options, the outcomes were: Chemotherapy OSm 8.3m and PFS 2.1m, Immunotherapy OSm 16.6m and PFS 11.4m and Targeted therapy OSm 21.7m and PFS 11.4m. Conclusions: Worldwide, there is no good quality scientific information to define the best specific treatment for acral lentiginous melanoma. Current available evidence suggests that treatment with targeted therapies such as c-kit, V600E or immunotherapy as some useful options. Link Prospero: CRD42020171528.[Table: see text]