Xiphophorus species, inbred strains, and interspecies hybrids have been used extensively to understand the genesis of melanoma and other types of malignancies. Despite sophisticated studies on the genetics of this model, biological studies have been limited by the availability of characterized cell lines. The authors have established a melanoma-derived cell line, XM, from the most commonly used interspecies hybrid model for studies of the genetics and cell biology of melanoma in Xiphophorus. This line demonstrated a previously unrecognized response to platelet-derived growth factor and exhibited a karyotype that was minimally aneuploid or possibly diploid. XM cells formed pigmented tumor-like masses when injected into zebrafish embryos. Some cells also migrated and exhibited differentiated pigment expression in a manner consistent with normal melanocytes. The XM cell is the first characterized line of known genetic background available for study of the in vitro biology of the Xiphophorus model.