Context: Acral lentiginous melanoma is the most prevalent clinical presentation of melanoma in ethnic groups other than whites and also occurs in significant numbers in North America and Europe. Despite a clear-cut clinical picture, histologic findings seen in partial biopsies may be too subtle and deceive pathologists dealing with such cases. OBJECTIVES: To make pathologists aware of the histologic findings during early phases of acral lentiginous melanoma (including the in situ phase), to compare those findings with what is seen in acral junctional nevus, and to highlight their similarities and differences. This review will also emphasize the important clinical and dermatoscopic findings to be considered when diagnosing acral lentiginous melanoma. DATA SOURCES: Review of published articles on the epidemiology; the clinical, dermatoscopic, and histopathologic findings; and the molecular biology of acral lentiginous melanoma as well as the personal experience ofs when dealing with such cases. CONCLUSIONS: Acral lentiginous melanoma is a clinicopathologic entity with a clear-cut clinical picture: a diameter larger than 0.7 mm; ill-defined, darkly pigmented, flat lesion with irregular borders on acral locations; and the presence of mostly single-cell proliferations of melanocytes along the dermo-epidermal junction. Along with a few additional criteria, these findings should be sufficient to allow the pathologist to make the diagnosis and to recommend complete excision. Fluent communication between clinician and pathologist will facilitate a correct diagnosis.