Hereditary melanoma in Xiphophorus hybrids carrying the melanoma-inducing Tu-Sd locus is caused by transcriptional activation of the Xmrk gene that resides at the Tu-Sd locus and encodes a novel member of receptor tyrosine kinases (RTK). In this study, a total of 27 hereditary melanomas from various hybrid genotypes harbouring 7 different Tu alleles were also found to over-express the corresponding Xmrk alleles. The level of over-expression correlated with the degree of malignancy of the melanoma. In addition, Xsrc expression was high in many malignant melanomas. Expression patterns and levels of the Xiphophorus EGF-receptor gene (Xerb B), the c-myc (Xmyc), and the PDGF (Xsis) gene(s) were not intriguing. Transcription of the ras gene(s) may be correlated to secondary events of melanoma progression. Expression patterns of Xfms, the Xiphophorus CSF-I receptor homologue, can be explained by different contents of infiltrating macrophages in the tumors. In carcinogen-induced tumors including one melanoma no significant expression of the Xmrk oncogene could be detected. Xsrc expression, however, was strikingly high. This indicates that activation of oncogenes other than Xmrk is instrumental in tumorigenesis of neoplasia of non-hereditary origin.