The criterion standard for diagnosing cutaneous melanoma continues to be histologic examination. However, classifying some melanocytic lesions by conventional microscopy can be problematic if they exhibit some architectural or morphologic characteristics of both nevus and melanoma. Moreover, histologic appearance does not always predict biologic behavior. There is therefore a need and opportunity to develop new technologies that can facilitate the histologic diagnosis of melanoma and potentially help distinguish lesions with a lesser or greater risk of metastasis. In part II of this 2-part continuing medical education article, we will review the molecular technologies currently available for facilitating melanoma diagnosis, including comparative genomic hybridization, fluorescence in situ hybridization, and epidermal genetic retrieval. Our goal is to provide the clinician with an up to date understanding of these molecular approaches so that they can be applied to their management of challenging melanocytic lesions.