Survival at 5 years of patients with localized primary malignant melanoma is about 80%, compared with a 35% survival in case of lymph nodes involvement. Sentinel lymph node(s) from 45 subjects with diagnosis of malignant melanoma stage I or II was/were studied with hematoxylin-eosin (HE), immunohistochemistry (IHC) and molecular biology (MB) techniques. The population was divided into three groups: HE-/IHC+/MB+, where 67% patients died; HE-/IHC-/MB+, where 57% died; and HE-/IHC-/MB-, where 100% of the patients are alive, with no lymphadenectomy and a median follow-up of 60 months. Those subjects who showed negativity with all the three methods had a null recurrence rate. Data herein obtained suggest a new molecular oncological staging, which would allow the selection of patients with submicroscopic metastases for a complete treatment. Moreover, several patients with no lymph node metastases should not undergo lymphadenectomies, and overtreatment could therefore be avoided.