Amelanotic malignant melanoma (AMM) often defies clinical diagnosis because of its wide range of clinical appearances and lack of pigmentation. Biopsy of AMM typically yields the correct diagnosis, although the histological findings, especially in metastatic lesions, occasionally may be confused with other malignancies. In cases histologically challenging, immunohistochemical techniques frequently provide diagnostic information. Multiple mechanisms to explain amelanosis have been suggested, all resulting in a single, common amelanotic phenotype. Appropriate studies to compare outcomes of amelanotic versus pigmented melanomas have not been performed. Treatment recommendations for AMM are identical to those for pigmented melanomas, although accurately defining clinical margins of the neoplasm often is challenging. Overall, a high index of suspicion and a low threshold to biopsy unusual clinical lesions ultimately may allow for earlier diagnosis and treatment of these frequently lethal malignancies.