High-energy, high-resolution synchrotron radiation diffraction was successfully used to measure the lattice misfit in the single-crystal nickel-base superalloy SC16. A three-peak model, one belonging to the precipitate phase γ′ and two to the matrix γ, was used to fit the diffraction peaks. Room-temperature (RT) contour plots and a temperature scan up to 1170 K revealed that the misfit evolves together with the measured thermal expansion difference between the γ and γ′ phases. This suggests that the origin of the misfit lies in the different thermal expansion coefficient of the two phases. The misfit was found to be positive at RT and to evolve toward negative values as the temperature increases.