The pathology of a disfiguring and debilitating fatal disease affecting a high proportion of the wild population of Tasmanian Devils (Sarcophilus harrisii) that was discovered is described. The disease, named devil facial tumour disease (DFTD), has been identified in devils found across 60% of the Tasmanian landscape. The prevalence of this disease was extremely variable, possibly reflecting seasonal trapping success. Between 2001 and 2004, 91 DFTD cases were obtained for pathological description. Grossly, the tumours presented as large, solid, soft tissue masses usually with flattened, centrally ulcerated and exudative surfaces. They were typically multi-centric, appearing first in the oral, face or neck regions. Histologically, the tumours were composed of circumscribed to infiltrative nodular aggregates of round to spindle-shaped cells often within a pseudocapsule and divided into lobules by delicate fibrous septae. They were locally aggressive and metastasised in 65% of cases. There was minimal cytological differentiation amongst the tumour cell population under light and electron microscopy. The diagnostic values of a number of immunohistochemical stains were employed to further characterise up to 50 representative cases. They were negative for cytokeratin, epithelial membrane antigen, von Willebrand factor, desmin, glial fibrillary acid protein, CD16, CD57, CD3 and LSP1. DFTD cells were positive for vimentin, S-100, melan A, neuron specific enolase, chromogranin A and synaptophysin. In conclusion, the morphological and immunohistochemical characteristics together with the primary distribution of the neoplasms indicate that DFTD is an undifferentiated neoplasm of neuroendocrine histogenesis.