This study shows that fluorescencein situhybridization (FISH) to thin sections cut from paraffin‐embedded material can lie used to distinguish between groups of melanocytic neoplasms and thus may be useful as an investigational and diagnostic tool. FISH with a probe for a repealed, alpha satellite sequence specific to chromosome 17 was used to investigate the chromosomal composition of dysplastic (or Clark's nevus) and Spitz's nevi and malignant melanomas. Hybridization was to thin (∼6 μm) sections cut from paraffin blocks. The number of signals per nucleus in normal diploid cells is expected to be less than 2 since the sections are thinner than one nuclear diameter. Keratinocytes and lymphocytes m these same sections showed 1–2 signals per nucleus with a mean of 1.2. Dysplastic nevi showed 1–4 hybridization signals per nucleus with a mean of 1.5. Spitz's nevi showed 1–2 signals per nucleus with a mean of 1.3. Melanomas showed 1–6 signals per nucleus with a mean of 2.1. We were thus able to use FISH to demonstrate differences in chromosome numbers between groups of benign and malignant melanocytic neoplasms. Technical improvements in the near future can be expected lo result in more precise estimates of chromo