N Context.-Histologic examination of clinically suspicious melanocytic lesions is very sensitive and specific for the detection of malignant melanoma. Yet, the malignant potential of a small percentage of melanocytic lesions remains histologically uncertain. Molecular testing offers the potential to detect the genetic alterations that lead to malignant behavior without overt histologic evidence of malignancy.Objective.-To differentiate benign melanocytic nevi from malignant melanoma and to predict the clinical course of melanocytic lesions with ambiguous histology using a novel genomic microarray.Design.-We applied a newly developed single-nucleotide polymorphism genomic microarray to formalin-fixed, paraffin-embedded melanocytic lesions to differentiate benign nevi (n = 23) from malignant melanoma (n = 30) and to predict the clinical course of a set of histologically ambiguous melanocytic lesions (n = 11).Results.-For cases with unambiguous histology, there was excellent sensitivity and specificity for identifying malignant melanoma with this genomic microarray (89% sensitivity, 100% specificity). For cases with ambiguous histology, the performance of this genomic microarray was less impressive.Conclusions.-Without microdissection and with quantities of DNA one-tenth what is required for more commonly used microarrays, this microarray can differentiate between malignant melanoma and benign melanocytic nevi. For histologically ambiguous lesions, longer clinical follow-up is needed to confidently determine the sensitivity and specificity of this microarray. Some of the previous technical hurdles to the clinical application of genomic microarray technology are being overcome, and the advantages over A pproximately 2% of the United States population (6 195 000 individuals) will be diagnosed with malignant melanoma during their lifetime.1 Rendering the diagnosis of malignant melanoma is currently a 2-tiered process beginning with a history and visual inspection and ending with a microscopic examination. This screening and confirmatory testing algorithm results in good sensitivity and specificity; however, several studies have demonstrated room for improvement.2-5 The seminal works by Bastian et al, 6,7 Dalton et al, 8 and Gerami et al 9 provided hope that adding a molecular test as a third tier for diagnostically challenging melanocytic lesions could increase both sensitivity and specificity and improve the accuracy of clinical prognostication. We analyzed archived formalin-fixed, paraffin-embedded (FFPE) skin biopsies of 64 melanocytic lesions (23 benign nevi, 27 primary malignant melanomas, 3 metastatic melanomas, and 11 melanocytic lesions of uncertain malignant potential [MLUMPs]) with a 330 000-probe single-nucleotide polymorphism (SNP) genomic microarray (GMA) to determine if gains and losses of chromosomal material could predict benign or malignant clinical behavior. Our results indicate that SNP-GMA is a sensitive and specific method for identifying malignant melanoma when the histology is unambiguous. For s...