Introduction Myeloid-derived suppressor cells (MDSCs) are key players in immunosuppressive mechanisms that lead to tumor escape and metastasis formation, both in human patients and murine models. The aim of this study was to compare the percentage of circulating MDSCs in dogs with cancer (group 1) to healthy controls (group 2) and dogs with non-neoplastic disease (group 3). Materials and Methods Whole blood samples of canine patients with cancer, healthy dogs and non-neoplastic diseases were prospectively collected. Peripheral blood mononuclear cells were isolated and MDSCs were labeled using CD11b, CD14 and MHC class II antibodies and quantified by flow cytometry. Medical records were reviewed to collect complete patients data. Wilcoxon Mann Whitney test was used to compare quantitative parameters. Results Thirty dogs were included in the group 1, 30 dogs in the group 2 and 15 in the group 3. The MDSCs median value was 20.9 [10.8;35.8] for group 1, 2.9 [1.0;9.5] for group 2, and 15.9 [7.1;31.8] for group 3. Group 1 had significantly higher percentage of MDSCs compare to group 2 (p<0.01). There was no significant difference between group 1 and 3 (p=0.36). Conclusion These results showed an increased percentage of circulating MDSCs in neoplastic dogs. MDSCs could therefore be an interesting biomarker for diagnosis and follow-up of dogs with cancer. Further studies are needed to assess the percentage of MDSCs as a specific tool for early diagnosis of metastasis.