Hybrids between certain species of the teleost Xiphophorus predictably develop melanomas. Classical Mendelian crossing experiments have allowed us to identify genetic loci involved in eliciting and in suppressing tumorigenesis. The overall picture is that melanoma formation results from functional elimination of a suppressor locus allowing abnormal expression of a melanoma locus. Melanoma formation in Xiphophorus behaves like a recessive trait. The fish melanomas consist of incompletely differentiated pigment cells and in many aspects resemble their murine and human counterparts. Cytogenetic studies of cells of the genetic melanomas have provided evidence for chromosomal abnormalities. In particular, cytogenetic manifestations of amplified DNA were detected in a cell line derived from a malignant melanoma. Amplified DNA was isolated and was found to be amplified in a particular type of genetic melanoma. Our results suggest that genetic changes in addition to elimination of suppressor genes contribute to the malignant phenotype of melanoma in Xiphophorus. It is possible that a similar situation occurs in cancers of higher vertebrates, including humans.