Seventy-eight melanoma patients and ten healthy individuals were examined. Follow up examinations of all melanoma patients were performed regularly on three months. Myeloid-derived suppressor cells (MDSC) were defined as lineage negative (CD3-, CD19-, CD56-), HLA-DR-/low, CD11b+ and CD33+. Classification of granulocytic (GrMDSC) and monocytic (MoMDSC) subsets was based on the CD15 and CD14 expression, respectively. Unlike the MoMDSC, that were present in 60% of healthy controls and 15% of melanoma patients, the GrMDSC were present in all examined participants, and the melanoma patients were found to have statistically higher frequencies compared with healthy controls. Accordingly, we kept focused on GrMDSC frequencies in relation to the melanoma stages and course of the disease. The GrMDSC values are highest in stage IV melanoma patients, with statistical significance compared to stages IA, IB, IIA, and IIB. Patients with progression had statistically higher GrMDSC counts comparing with those with stable disease (p=0.0079). Patients who had progression free interval (PFI)<12 months showed significantly higher GrMDSC values compared to those with PFI>12 months (p=0.0333). Granulocytic MDSC showed significant negative correlation with PFI intervals (p=0.0095). The granulocytic MDSC subset was predominant in all our patients. We confirmed that GrMDSC do accumulate early in the peripheral blood of melanoma patients and their frequencies correlate narrowly with the clinical stage and the spread of the disease. Increase in GrMDSC frequencies correlates well with a progressive disease and could be considered as a potential predictive biomarker of high risk melanoma cases that are more likely to have a shorter PFI.