Melanoma is considered on cytology the great pretender. In fact, neoplastic cells may vary in shape ranging from round to polygonal and spindle.

This can make the diagnosis very difficult, in particular in amelanotic forms, where melanin granules are either absent or present in very low numbers. In those cases, a definitive diagnosis may require further testing and in particular immunocytochemical stains (ICC).
On a publication from 2015 on 38 cases of canine oral neoplasms, the combination of cytology and ICC (cytokeratin, vimentin, and Melan A) showed a very high sensitivity and specificity for the presurgical diagnosis of amelanotic melanoma. Early identification of this tumour is considered crucial from a clinical point of view, as ability to metastasise to local lymph nodes and other organs is significantly higher than other oral tumours. Treatment involves local tumour control through surgery and/or radiation therapy, as well as systemic treatment.