SUMMARY Objectives: Immunohistochemical methods and molecular diagnostic methods have been used to examine the role of three groups of regulation: changes in the genetic material and signalling pathways of the melanoma cell, regulation by the immune system, and regulation by the enzyme of the tumour microenvironment. Patients and methods: From a representative part of the melanoma tissue, 3 cylinders with a diameter of 1 mm were used for the preparation of tissue microarrays (TMAs). The study included 39 biopsies of primary melanoma (Breslow < 1.5 mm), 42 samples of primary melanoma (Breslow > 1.5 mm) and 31 samples of metastatic melanoma. In addition to determining the expression of the PD-1 and PD-L1 molecules, by immunohistochemical staining of the CD3 molecule we identified tumour infiltrating lymphocytes (TILs). Furthermore, we examined the presence of CD8+, CD4+ Foxp3+ and CD20+ B lymphocytes. TIL is classified into BRISK categories. The relationship between the expression of MITF, cyclin D1 and Bcl-2 proteins, as well as the metalloproteinase (MMPs) enzymes, and the investigated molecules has been determined. The genetic rearrangement of the MITF gene was analysed using the qReal-time PCR method. Results: PD-1 and PD-L1 are more strongly expressed in melanomas categorized as Breslow > 1.5 mm. The expression of PD-1 and PD-L1 almost always > 50% when TIL is in BRISK B category. We did not prove the dominant presence of certain lymphocytes (CD8+, CD4+ or Treg) in any of the TIL categories. We proved a statistically significant correlation of expression of PD-1 and PD-L1 proteins with expression of cyclin D1 in the cell nucleus and MITF, as well as Bcl-2 proteins in the cytoplasm of tumour cells (p< 0.001). The difference in PD-L1 expression was statistically significant, depending on whether MITF amplification was present, in the metastasis group (p=0.008). No correlation was found between the expression of MMPs and the expression of PD-1 and PD-L1 (p=0.723). Conclusion: The expression of proteins involved in the PD-1/PD-L1 signalling pathway is regulated by the interaction of the melanoma cell and the immune system cells. It depends on the location of the lymphocytes and the density of the TIL, not on their type. The expression of PD-L1 is dependent on the activity of the MITF factor and its target proteins, the cell cycle regulators.