Pagetoid proliferation of single melanocytic cells or small nests of melanocytes may be seen in a variety of melanocytic neoplasms including pagetoid spitz nevi, de novo epithelioid melanocytic dysplasia, and melanoma. Distinction of these entities may be difficult as there is considerable clinical and histologic overlap in these entities. Patient outcome and management may be significantly influenced by the pathologists' impression. In this study, we collected 24 cases of superficial melanocytic neoplasms with prominent pagetoid melanocytosis. We allowed 3 experienced consultant dermatopathologists to independently evaluate these entities and score them from 1 to 4, with 1 being totally benign and 4 being melanoma. In addition, we performed fluorescence in-situ hybridization (FISH) using a new melanoma FISH assay targeting 6p25, 6q23, Cep6, and 11q13. We found strong interobserver reliability in the diagnosis in 71% of cases, whereas 29% showed considerable discordance. We found that FISH accurately identified as malignant 5 of 7 cases which had a consensus diagnosis of melanoma. None of the cases with a consensus diagnosis of benign were FISH positive. Two of 11 cases considered indeterminate by the judges were positive by FISH. One of these 2 cases showed definitive histologic changes of melanoma on later complete re-excision. There is considerable discordance in superficial melanocytic neoplasm with prominent pagetoid melanocytosis even among expert consultants. There is likely a subset of such cases where FISH can play a significant role as a diagnostic aid.