Regulatory protein S100A2 is localized in the cell nucleus and takes part in the regulation of the cell cycle and cancerogenesis. It belongs to a large family of S100 proteins and can simultaneously bind calcium and zinc ions. Using a direct thermodynamical method of isothermal titration calorimetry we have determined that in the absence of calcium ions the S100A2 can bind three zinc ions per each monomer. Besides that, it was determined that the thermodynamics of zinc binding to different binding sites on the S100A2 are significantly different. Zinc binding to the first two sites on the S100A2 is enthalpically unfavorable and is driven only by entropic factors, while binding of the third zinc ion is enthalpically favorable. Analysis of the zinc ion adsorption isotherms shows that their binding occurs in a consecutive order.