An investigation of the invasiveness of avian neural crest cells and neural crest-derived melanocytes through a human amniotic basement membrane (BM) was undertaken. Avian neural tube explants or derived melanocyte populations were seeded directly onto BMs in membrane invasion culture system (MICS) chambers for periods of 24, 48, and 72 h. In 36 experimental trials for each group, neither neural crest nor neural crest-derived melanocytes were observed to have invaded the BMs. In concert with these studies, coculturing of B16F10 murine melanoma cells with avian neural crest-derived melanocytes was performed in MICS chambers. Under these experimental conditions, the neural crest-derived melanocytes were able to successfully invade the BMs and to a greater extent than the B16F10 tumor cells. These data suggest that neural crest cells and neural crest-derived melanocytes do not have the ability to invade the BM alone; however, they can be induced to be invasive when cocultured in the presence of B16F10 cells. Alternatively, the B16F10 cells may create weaknesses within the BM that facilitate migration of the pigmented crest cells.