The X-ray crystal density method uses silicon spheres highly enriched in 28Si as a primary method for the dissemination of the SI base unit kilogram yielding smallest possible uncertainties associated with the mass m within a few parts in 10−8. This study compares different available and newly developed analytical methods and their results for the determination of the molar mass M of silicon highly enriched in 28Si (Me) and of silicon (Mx) with an almost natural isotopic distribution. While for Me relative uncertainties urel(Me) in the lower 10−9 range are obtained routinely, it was not possible to fall below a value of urel(Mx) < 4 × 10−6 in the case of natural silicon, which is approximately three orders of magnitude larger. The application of the state-of-the-art isotope ratio mass spectrometry accompanied with sophisticated thoroughly investigated methods suggests an intrinsic cause for the large uncertainty associated with the molar mass of natural silicon compared to the enriched material.