To characterize the possible cytogenetic link between a primary tumor and its metastasis, interphase cytogenetic analysis was performed on tumor cells and cutaneous metastasis from a male patient with malignant melanoma by using fluorescence in situ hybridization. The numbers of distinct hybridization domains specific for ten different pericentromeric sequences were used as indicators of copy numbers of these chromosomes. In the primary tumor, the majority of cells had two copies of these chromosomes, but significant numbers of nuclei also were present with one and three copies. In addition, in almost all cells, both sex chromosomes were abnormal; nullisomy of the Y chromosome was associated with X disomy. The corresponding metastatic tumor cells were predominantly monosomic; only the distribution of chromosomes 11 and 7 was similar to the primary tumor. In the metastatic tumor, the sex chromosomes had a normal copy number; that is, one Y and one X were detected. These data indicate that both the initiation and the progression of this melanoma are associated with chromosome losses.