Congenital giant nevi are complex cutaneous malformations composed of melanocytic and occasionally neural supportive elements. Malignant neoplasms arising in this setting are not uncommon, and their histologic appearances often differ significantly from the typical pattern of malignant melanoma. We report six patients with neoplasms arising in congenital giant nevi and one patient with a neoplasm arising in an extensive congenital blue nevus, and present a description of the neoplastic patterns encountered. These patterns include 1) poorly differentiated small round cell cancer, 2) malignant cellular blue nevus, 3) spindle-cell malignant tumor with lamellar cell (pseudomeissnerian) differentiation, 4) so-called minimal deviation melanoma, 5) heterologous malignant mesenchymal differentiation including rhabdomyosarcoma and liposarcoma, and 6) undifferentiated spindle cell cancer. We have reviewed the literature in order to address the question of frequency of malignant transformation in congenital giant nevi, the reported experience with the morphology of these cancers, and the histogenesis of these sometimes complex neoplasms as it is illuminated by our current understanding of the embryology of the neural crest.