Plasma exosome-derived SENP1 levels in melanoma patients with tumor size >10 cm, located in the mucosa or viscera, with Clark level IV/V, with lymph node metastasis, and TNM stages IIb–IV were significantly higher than in patients in with tumor size <10 cm, located in the skin, with Clark level I–III, without lymph node metastasis, and TNM stages IIb–IV (all P < 0.05). This evidence concerns the gene SENP1 and metastatic malignant neoplasm in the lymph nodes.