Cutaneous Melanoma (CM) commonly is a tumor arising from the incidence of genetic mutations in melanocytes, the pigment generating cells, which can occur in different parts of the body such as skin, eye, inner ear, and leptomeninges. CM incidence has considerably been increasing around the world (1–4). However, melanoma constitutes about 1% of all skin malignancies. CM is the most aggressive tumor with the highest mortality rate among skin cancers (5). This prevalence probably yields a lifetime risk of 1 in 24 individuals for developing any type of CM. Among the registered cancers, CM is the fifth most common in males and the sixth most common in females. Further, men are at 40% more risk than women to develop invasive CM in their lifetime (6, 7). About 91,270 cases of CM have been identified in 2018 alone, leading to 9320 deaths (8). Different risk factors for the development of CM consist of UV exposure, male sex, immunosuppression, age increase, genetic predisposition (skin phenotype), genetic mutations, inflammatory bowel disease, and phosphodiesterase-5 use (9–13). According to the characteristics of the tumor (location, stage, and genetic profile), the therapeutic methods may be surgical resection, chemotherapy, radiotherapy, Photodynamic Therapy (PDT), immunotherapy, or targeted therapy. Currently, for patients with stage I–IIIB malignant CM, surgery is the mainstay of therapy (13–16). The surgical management of regional Lymph Nodes (LNs) for all patients with CM has been controversial since 1892 when H. Snow first recommended Elective Lymph Node Dissection (ELND) as a method to prevent tumor progression regardless of the presence of clinical regional nodal metastases (17, 18). The main shortcoming of ELND is that only about 20% of patients with middle-thickness primary CM are evaluated to have metastases in the regional lymph nodes, whereas 80% of patients are exposed to the morbidity of lymphadenectomy without the real benefit (19). Moreover, several randomized trials have failed to show an overall survival (OS) benefit for ELND (20–23). In recent decades with the introduction of sentinel lymph node biopsy (SLNB), ELND has mainly been replaced (24, 25). As metastases from CM significantly progress in LNs, SLNB has emerged as a major diagnostic tool for determining whether cancer has developed beyond the early tumor site to the LNs (26). Therefore, SLNB with lymphatic mapping was developed as a minimally invasive surgical procedure and sensitive prognostic method to stage clinical regional LNs without the associated morbidity of ELND (18, 19). This is the surgical technique by which the sentinel LNs are removed and checked for the presence of cancer cells. SLNB was developed in order to determine early metastases in clinical regional LNs and to screen only patients with nodal metastases to candidate complete lymph node dissection (CLND) and to prevent this in patients without nodal metastases. The false-negative rate of SLNB ranges from 10 to 20% (27, 29). Most surgeons commonly advise the triple manner, which includes preoperative lymphoscintigraphy, perioperative injection of blue dye (isosulfan blue or methylene blue), and intraoperative gamma probe identification. The accuracy of this procedure is approximately 99% (19). Presently, several experts advocate SLNB for tumor stages Ib and II (30). Recent research has shown that the overall occurrence of positive SLNs in patients undergoing SLNB is approximately 15 -20%. In addition, this range relies on the primary tumor thickness: 35-40% of T4 tumors and 5-7.8% of T1 lesions (31–33). Further, several other predictive factors are correlated with increased risk of SLN involvement in patients with localized CM, including Breslow thickness, Clark level, ulceration state, angiolymphatic invasion, tumor location, high tumor mitotic rate (TMR), and young age (19, 34–37). Furthermore, the local, regional, systemic recurrence and survival rates in CM are all strongly correlated with Breslow thickness (38). The aims of this article were to evaluate the predictive factors of SLN positivity in CM and to provide a model to predict SLN status for the optimal surgical management of these patients.