A 6-year-old female black-tailed prairie dog (Cynomys ludovicianus) was presented with a space-occupying lesion in the left submandibular region. On computed tomography, a low attenuating, poorly circumscribed mass infiltrated the left mandibular bone, with osteolytic change. Microscopically, the lesion was composed of odontogenic epithelium proliferating in nests and embedded in abundant dental papilla-like ectomesenchyme, including dentine and enamel. Multifocal amyloid deposition was observed. Immunohistochemically, the neoplastic epithelial cells were positive for cytokeratin (CK) AE1/AE3, CK14 and p63. Some epithelial cells were positive for amelogenin and some adjacent to the amyloid deposits co-expressed S100. The ectomesenchymal cells expressed vimentin and strong S100 immunoreactivity was observed in odontoblast-like cells. The amyloid was immunolabelled with amelogenin. The tumour was diagnosed as amyloid-producing odontoameloblastoma.