Since 2012, brown bullhead catfish (Ameiurus nebulosus) in a lake that spans Vermont, USA, and Quebec, Canada, have shown a high rate of melanomas, suggesting a causal contaminant or contagion1. We tested the hypothesis that this affliction represents a clonally transmissible cancer, a rare phenomenon in which cancer cells themselves spread between individuals, behaving more like parasites than conventional tumours2. Whole-genome sequencing of tumour and matched non-tumour host tissues revealed that tumour mitochondrial and nuclear genomes are more closely related to each other than to their hosts or unaffected fish. Hundreds of thousands of genetic variants are shared among tumour samples but are absent from host fish, vastly exceeding levels seen in conventional cancers3. These findings indicate that melanoma in these brown bullheads represents the fourth documented type of naturally occurring transmissible cancer in animals, after dogs4, Tasmanian devils5 and several bivalve species6–13. This raises important questions about the cancer’s origin, the mode of transmission and the long-term impact on fish populations.