In Switzerland, the Opalinus Clay unit was chosen as host rock for a repository for nuclear waste and has recently been investigated in a deep drilling campaign at possible repository construction sites. X-ray images of drill cores were compiled into virtual rock columns and were statistically analyzed with respect to layered compositional variations. This provides insight into scale-dependent homogenization and improves sampling strategy. To predict the repository behavior, using continuum-based models of Opalinus Clay, requires the knowledge of effective properties related to a minimum volume at which Opalinus Clay behaves homogeneously. It turned out that with respect to rock composition, such a volume does not exist in the sense that a single sample of manageable size provides a reliable mean composition. This is because the variation of the cm to dm thick layers, which differ in composition, does not sufficiently homogenize even at the 10-m scale. Thus, effective properties must be obtained by averaging several handleable samples. Regarding the composition of Opalinus Clay at a particular location, about 30 samples, distributed over the whole thickness, with a length of about 30 cm should be measured so that the relative error of the mean value is not higher than 5%–10%. For the statistical analyses computed tomography (CT) values of X-ray data were calibrated with respect to rock composition based on laboratory measurements. The CT values are largely controlled by the respective volume fraction of calcite, quartz, and porous clay matrix. These three components form >80 vol% of the sedimentary rocks studied (also above and below Opalinus Clay). The relationship between CT value and component contents depends on the rock type. The use of data from different rock types to calibrate CT values with respect to composition can lead to erroneous results.