Although nanoscale multilayers are often used for the determination of interdiffusion coefficients at low temperatures, knowledge of the impact of the microstructure on measurements is limited. In the present study, we measure the interdiffusion coefficient in fcc Ni--Cr at 440\degree C using multilayers consisting of alternating layers of pure Ni and Ni20Cr (wt.\%), with a nominal wavelength of 4.5 nm. Three techniques were used to characterize the evolution of the multilayers with annealing: atom probe tomography (APT), energy-dispersive X-ray spectroscopy (STEM-EDX) and X-Ray reflectivity (XRR). Each of the three techniques allowed to determine an interdiffusion coefficient. The results evidence that the interdiffusion coefficient is dependent from the technique used to measure it. The primary cause is a very complex microstructure resulting from the elaboration method used to obtain the fine concentration modulation. The analysis of atom probe tomography volumes reveals a high density of columnar grain boundaries with extended chemical widths. A model was derived, allowing to dissociate the contribution of diffusion along and perpendicularly to grain boundaries. The present results could serve as guides for future diffusion investigations involving multilayers.