—Based on experimental data (T = 650–800 °C, P = 1–2 kbar) on the solubility of columbite and tantalite in silicate melt and on the distribution of Ta and Nb among coexisting silicate melt, aqueous fluid, and aluminum fluoride melt, we calculated a possible change in the Ta/Nb indicator ratio in residual deeply differentiated granite melts. The Clarke values of these metals in acid rocks of the Earth’s crust were taken as their initial contents. The calculations were made by the mass balance method. It is shown that the separation of fluid in the closed magmatic system rock-forming minerals–silicate melt–water can lead to an approximately twice increase in Ta/Nb in the residual melt as compared with the initial Clarke value. In the system rock-forming minerals–silicate melt–aluminum fluoride melt with the initial content of fluorine close to that in biotite granites, the Ta/Nb ratio in the residual melt can increase to ~1. Successive crystallization of minerals of the isomorphic columbite–tantalite series can lead to Ta/Nb > 2 in the residual melt. Crystallization of biotite causes a significant increase in Ta/Nb and prevents the accumulation of these metals in the residual silicate melt.