Observations of extragalactic objects need to be corrected for Galactic absorption and this is often accomplished by using the measured 21 cm HI column. However, within the beam of the radio telescope there are variations in the HI column that can have important effects in interpreting absorption line studies and X-ray spectra at the softest energies. We examine the HI and DIRBE/IRAS data for lines of sight out of the Galaxy, which show evidence for HI variations in of up to a factor of three in 1 degree fields. Column density enhancements would preferentially absorb soft X-rays in spatially extended objects and we find evidence for this effect in the ROSAT PSPC observations of two bright clusters of galaxies, Abell 119 and Abell 2142. For clusters of galaxies, the failure to include column density fluctuations will lead to systematically incorrect fits to the X-ray data in the sense that there will appear to be a very soft X-ray excess. This may be one cause of the soft X-ray excess in clusters, since the magnitude of the effect is comparable to the observed values.
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