Introduction: Histological grading and cell proliferation markers are typically used to predict post-surgical prognosis of cutaneous mast cell tumours (MCTs). Material and methods: In the present study, sixty MCTs underwent histological evaluation, grading, immunohistochemistry and total RNA isolation by Real Time RT-PCR, for Ki-67, Bcl-2 and Cox-2. Results: Ki-67 protein was significantly associated with tumour grade and prognosis. Bcl-2 mRNA was associated with the tumour grade and prognosis: the probability of dying for dogs with mRNA > = 0.22 was 5 times higher than dogs with a lower value. The Cox-2 protein was expressed in 51 out of 60 MCTs (85%), and a significant increase in the gene expression was observed, but no association with tumour grade and prognosis was detected. Discussion: These results confirm the prognostic role of Ki-67 protein, and suggest the possible role of Bcl-2 gene in MCT progression. The Cox-2 mRNA up-regulation and the protein expression would suggest a role of Cox-2 in MCTs pathogenesis. Further investigations are required to evaluate the prognostic and therapeutic implications of Cox-2 expression in canine MCTs.