The biopsy lies at the heart of the management of the suspected melanocytic neoplasm. Dermatologists are the ideal physicians to examine patients with suspect melanocytic lesions and an understanding of when and how to perform a biopsy is vital. Various algorithms have been formulated to allow for facilitation of the clinical examination, including the ABCDE rule, the Glasgow 7-point checklist, and the “ugly duckling” sign. Along with this, dermoscopy can increase the sensitivity of diagnosis. Proper training regarding dermatoscopy is essential, especially with algorithms such as the Menzies method, the 7-point checklist, and pattern analysis. Digital photography and digital dermatoscopy allows for surveillance of suspect nevi or patients with multiple nevi. For neoplasms suspected of being melanoma, an excision for diagnosis with 1- to 3-mm borders is ideal, although a shave, punch, or other incisional biopsy can be performed in special circumstances. Finally, research has allowed for promising technologies including gene profiling of tape-stripped samples along with automated software analysis of digital dermatoscopic images.