Histologic analysis remains the gold standard for diagnosis of melanoma. The pathology report should document those histologic features important for guiding patient management, including those characteristics on which the diagnosis was based and also prognostic factors. Pathologic examination of sentinel lymph nodes provides very important prognostic information. New techniques, such as comparative genomic hybridization and fluorescence in situ hybridization are currently being studied to determine their usefulness in the diagnosis of melanocytic lesions. Recent molecular studies have opened new avenues for the treatment of patients with metastatic melanoma (ie, targeted therapies) and molecular pathology is likely to play an important role in the emerging area of personalized melanoma therapy.