Metals in the neutral Interstellar Medium (ISM) of galaxies are crucial for the formation and evolution of galaxies, stars, cosmic dust, molecules, and planets. However, understanding the metal abundances in the neutral ISM is complicated by the presence of cosmic dust. Large quantities of metals are missing from the observable gas-phase because they are incorporated into dust grains. This phenomenon is called dust depletion. Until recently, the metallicity of the neutral ISM in the vicinity of the Sun was assumed to be Solar. In this paper we directly measure the metallicity of the neutral ISM, by quantifying dust depletion without making as- sumptions on the gas metallicity, using Hubble Space Telescope (HST) and Very Large Telescope (VLT) spectra of 25 hot bright stars. We find that the dust-corrected metal- licity in the neutral ISM in our Galaxy is not always Solar, but shows large variations spreading over a factor of 10 and including many regions of low metallicity, down to ∼ 17% Solar and possibly below. Pristine gas infalling towards the Galactic disk in the form of intermediate and high-velocity clouds could cause the observed chemical inhomogeneities on scales of tens of pc. This has a profound impact for the chemical evolution of galaxies.