Melanoma is a tumor that continues to increase in both the number of cases presenting and mortality. Patients with disease that has spread beyond the cutaneous boundary still suffer from significant morbidity and mortality despite advances in immune therapy. It is incumbent that clinicians keep up with the latest advances in both tumorigenesis and metastatic capabilities, and be aware of clinical, histopathologic, and genetic metrics to assist in the early diagnosis of aggressive tumors. This review synopsizes some of the most recent findings. J Drugs Dermatol. 2022;21(12):1289-1293. doi:10.36849/JDD.6814.