We analyzed the karyotypes of nine established human malignant melanoma cell lines derived from two female and six male patients. Each of the cell lines had an aneuploid stemline chromosome number. Analysis of G-banded chromosomes identified a number of altered (marker) chromosomes in these cell lines; in all the lines, chromosome 6 was found to be involved in the marker chromosomes. A review of the literature and these cases showed that of 47 cell lines or primary melanoma cells karyotyped, 38 (80.8%) had a marker involving the 6. We believe that the genetic factor determining melanoma initiation is located in the distal segment of 6q. Deletion of this segment or the entire 6q is responsible for the cell’s (melanoblast or melanocyte) becoming malignant. The proximal segment of 6q and 6p can be involved in marker formatio