Morphologic heterogeneity among melanocytic proliferations is a common challenge in the diagnosis of melanoma. In particular, atypical melanocytic lesions in children, adolescents, and young adults may be difficult to classify because of significant morphologic overlap with melanoma. Recently a four-probe fluorescence in situ hybridization (FISH) protocol to detect chromosomal abnormalities in chromosomes 6 and 11 has shown promise for improving the classification of melanocytic lesions. We sought to determine the correlation between FISH results, morphology, and clinical outcomes in a series of challenging melanocytic proliferations in young patients. We retrospectively performed the standard four-probe FISH analysis on 21 melanocytic neoplasms from 21 patients younger than 25 years of age (range 5–25 years, mean 14.6 years) from Stanford University Medical Center who were prospectively followed for a median of 51 months (range 1–136 months). The study cohort included patients with 5 confirmed melanomas, 2 melanocytic tumors of uncertain malignant potential (MelTUMPs), 10 morphologically challenging atypical Spitz tumors (ASTs), and 4 typical Spitz nevi. FISH detected chromosomal aberrations in all five melanomas and in one MelTUMP, in which the patient developed subsequent lymph node and distant metastasis. All 10 ASTs, 4 Spitz nevi, and 1 of 2 MelTUMPs were negative for significant gains or losses in chromosomes 6 and 11q. Our findings demonstrated a strong correlation between positive FISH results and the histomorphologic impression of melanoma. This finding was also true for the MelTUMP with poor clinical outcome. Therefore FISH may serve as a helpful adjunct in the classification of controversial melanocytic tumors in young patients.