We identified a group of melanocytic lesions with an architectural pattern very similar to that of a junctional nevus: cells mostly grouped in distinct nests, more or less of the same size and shape, and regularly distributed along the dermoepidermal junction. In contrast with these nevus-like features, these neoplasms display additional details which are incompatible with a diagnosis of junctional nevus. These include areas of lentiginous array with focal pagetoid spread of melanocytes above the junction; marked cytological atypia, such as nuclear enlargement, hyperchromasia, nuclear membrane thickening and with a mild degree of cellular pleomorphism. Moreover, these lesions mostly developed on severely sun-damaged skin of old patients. Using a four-probe fluorescence in situ hybridization (FISH) assay targeting RREB1, MYB, Cep6, and CCND1, we found that seven of the eight propositus cases showed chromosomal aberrations consistent with the standardized FISH diagnostic criteria for melanoma. Instead, the five junctional nevi that served as controls were negative in this test. These findings underline the utility of correlating clinical-pathological observations with FISH analysis for diagnosing correctly as melanoma these malignant neoplasms, which closely simulate a junctional nevus.