The chemotherapy and photon radiotherapy are the most often applied methods in treatment of the cancer diseases because of their effectiveness and high cure rates. Apart from eligible destruction of the tumour, one of the side effects of these treatment methods is possible modification of main and trace element concentration in different human tissues and fluids. In this paper, the copper (Cu) level in human serum was determined by total reflection X-ray fluorescence method in 142 chemotherapy patients and in 44 healthy persons being a control group. The Cu concentration in the chemotherapy group was found to be on the level 1.78 ± 0.909 mg/L, while in the control group, it was 1.08 ± 0.551 mg/L. Performed measurements allowed for calculation of the parameters of copper concentration distribution (mean value, standard deviation, median) for both analysed groups. The theoretical nature of the concentration distribution was tested and found as a log-normal distribution (control group) and a log-stable distribution (chemotherapy group). The copper concentration distributions for both studied group were statistically compared using Kolmogorov-Smirnov test, and the conclusion was that the distributions are statistically different. Serum Cu levels were significantly higher in the chemotherapy group than in the control group. Taking into account the results for the control group, the copper concentration reference quantile ranges in human serum were obtained. The values of the mean, median and other quantiles determined in this case can be applied in two-group comparison studies. The obtained results can be used as a diagnostic tool for chemotherapy patients.