Fluorescence in-situ hybridization (FISH) has arisen as a novel ancillary test for the pathological diagnosis of melanoma. It is an outgrowth of studies using comparative genomic hybridization, a technique capable of surveying the entire genome for DNA copy number changes. An original report published in 2009 showed high sensitivity (87%) and specificity (95%) for diagnosing melanoma, using a combination of 4 FISH probes that target 6p25 (RREB1), 6q23 (MYB), 11q13 (CCND1), and chromosome 6 centromere. Since then, a number of studies have been published, supporting the high accuracy of FISH for diagnosing melanoma. In addition, various clinicopathological settings where FISH may be particularly useful are explored. FISH tests for melanoma are now commercially available. Meanwhile, questions have been raised by some about the true diagnostic value of FISH, particularly in melanocytic lesions with ambiguous histopathology. This review will briefly introduce the historical development of FISH for melanoma diagnosis and discuss its diagnostic value as well as its potential limitations at present.