A thirteen-year-old patient, diagnosed with melanoma was followed cytogenetically using short-term cultures of specimens from a subcutaneous nodule, lymph node, and brain metastases. Simple hypodiploid karyotypes with loss of heterozygosity for chromosomes 5, 9, 10, 16 and 17 and two structural changes in 3 and between 13 and 21 increased in complexity to near triploid in the lymph node. Two cell types of the lymph node showed a progression of structural rearrangements prior to metastasis to the brain. Translocation of 6p to chromosome 2, deletions of 8, and a translocation (2;19) preceded p and q arm deletions of both chromosomes 9 and 11 in the lymph node. Cells metastasizing to the brain showed the accumulation of all previous aberrations and had acquired a direct duplication of distal 17 long arm. Whether or not elevated levels of protein kinase C, located on chromosome 17q contribute to tumor adhesion and growth on the brain remains to be elucidated. Identification of most chromosomes undergoing rearrangement was carried out using whole chromosome painting probes in in situ hybridizations. Some of these rearrangements would have been impossible to identify by standard karyotyping.