According to the American Joint Commission on Cancer (AJCC) 8th edition guidelines, SLN biopsy is recommended for primary melanomas with a Breslow thickness of at least 1 mm. Additionally, the National Comprehensive Cancer Network (NCCN) recommends that a SLN biopsy may be considered for melanoma patients with T1b lesions, which are 0.8-1 mm thick or less than 0.8 mm thick with ulceration. It can also be considered for T1a lesions that are less than 0.8 mm thick but have other adverse features, such as a high mitotic rate, lymphovascular invasion, or a positive deep margin. To reduce the false negative rate of melanoma SLN biopsy, we have introduced the intraoperative use of Sentinella, a gamma camera, to enhance the identification rate of SLNs beyond that of the traditional gamma hand-held probe. At the Center for Melanoma Research and Treatment at the California Pacific Medical Center, a multidisciplinary approach has been established to treat melanoma patients when the diagnosis of primary melanoma is made with a referral to our melanoma center. This comprehensive approach at the melanoma tumor board, including the efforts of pathologists, radiologists, dermatologists, surgical, medical and radiation oncologists, results in a consensus to deliver personalized and high-quality care for our melanoma patients. This multidisciplinary program for the management of melanoma can be duplicated for other types of cancer. This article consists of current knowledge to document the published methods of identification of sentinel lymph nodes. In addition, we have included new data as developed in our melanoma center as newly published materials in this article to demonstrate the utility of these methods in melanoma sentinel lymph node surgery. Informed consent has been waived by our IRB regarding the acquisition of clinical data as presented in this study.