OBJECTIVE: Increasing HIFs in malignant melanoma, the highly aggressive skin tumour, results in the stimulation of invasiveness. Increased HIF-1α fallouts in inhibition of the activity of some mitochondrial enzymes and leads to preference of cytosol energetic metabolism. Increase of aerobic glycolysis is reflected in an increase of free NADH (Warburg effect) and develops the malignant melanoma.Our goal was to find a link between hypoxia, or hypoxia mimicking factors and the stage of malignant melanoma. Furthermore, we focused on the finding of the experimental parameter which could monitor melanoma patients. PATIENTS AND METHODS: We targeted HIF-1α gene expression and VDR rs2107301 gene polymorphism by PCR analysis. We detected the level of NADH in blood plasma by fluorescence spectroscopy (excitation and emission spectra). RESULTS: Analysis of the obtained data from patient samples has shown an increase in HIF-1α which correlates with the disease stage. Investigation VDR rs2107301 polymorphism of patient samples does not show any significant changes in single nucleotide polymorphism, and the low vitamin D level in blood is not a result of VDR mutation in mitochondria. NADH levels vary under hypoxic and pseudohypoxic conditions and refer to the cancer stage. CONCLUSIONS: The apparent mismatch between HIF-1α expression and NADH fluorescence has become the basis for the design of an algorithm for monitoring malignant melanoma based on the sensing of NADH fluorescence and the determination of HIF-1α.