<p>Melanoma is an aggressive form of skin cancer. Its histopathological diagnosis may be challenging and subject to significant inter- and intraobserver variability. It is also a disproportionate source of pathology malpractice lawsuits worldwide. The knowledge base on melanocytic lesions is rapidly expanding, with many recent novel classification systems, therapies and molecular targets. Hence, specimens diagnosed or suspected as melanocytic lesions should be carefully and appropriately sampled, fixed, processed and analyzed to achieve the best possible patient treatment, follow-up and counseling. Herein, we describe common important dermoscopic terms and findings, standard biopsy procedures, preanalytical procedures, microscopic criteria, useful immunohistochemical markers, predictive and diagnostic molecular findings and other ancillary tests related to melanoma diagnosis, therapy and prognostication. This article is part of a larger project from the Brazilian Society of Pathology that proposes best practice recommendations for pathologists and clinicians in different fields.</p>