A giant congenital pigmented nevus was observed in a newborn male. A melanocyte culture was established from nevus fragments removed at age 6 days. Analysis of 136 metaphases harvested from the primary culture showed 74% normal mitoses, 22% polyploids, and 4% mitoses with chromosome rearrangements involving in particular 1p, 12q, and 19p. In addition, the culture showed a high level of HLA-DR expression. Although histology showed no sign of malignancy, these findings may illustrate one of the first events which might eventually progress toward malignancy.