Gene expression analyses have been recently used in cancer research to identify genes associated with tumourigenesis and potential prognostic markers and therapeutic targets. In the present study, the transcriptome of dogs that had died because of mast cell tumours (MCTs) was characterised to identify a fingerprint having significant influence on prognosis determination and treatment selection. A dataset (GSE50433) obtained using a commercial canine DNA microarray platform was used. The transcriptome of seven biopsies obtained from dogs with histologically-confirmed, surgically-removed MCT, treated with chemotherapy, and dead for MCT-related causes, was compared with the transcriptional portrait of 40 samples obtained from dogs with histologically-confirmed, surgically-removed MCT that were still alive at the end of the follow-up period. Among the differentially expressed genes (DEGs), eight transcripts were chosen to validate DNA microarray results by quantitative real time PCR; then, their mRNA levels were measured in a cohort of 22 additional MCTs. Statistical analysis identified 375 DEGs (fold change 2, false discovery rate 5%). The functional annotation analysis provided evidence of drug metabolism and cell cycle pathways. Particularly, members of solute carrier transporter (SLC) and UDP glucuronosyltransferase (UGT) gene families were identified as targets. The principal component analysis of the 22 additional MCTs identified in a separate cluster dogs dead for MCT-related causes. SLCs and UGTs have been recently recognised in human cancer as important key factors in tumour progression and chemo-resistance. An in-depth analysis of their role in aggressive canine MCT might be useful in future studies.