Theory of sampling offers powerful tools for process optimization. An adequate sampling interval can be determined for spectral measurements when utilizing a multivariate extension of variography by applying score vectors as independent sources of uncertainty. The traditional way is to apply variographic analyses into single process variables independently. In the multivariate extension, those process variables are replaced with score vectors of principal component analysis. The combined uncertainty found this way depends not only on the variance in the spectra, but also, for example, on the number of utilized score vectors and the preprocessing method. This approach is illustrated with a crystallization process continuously followed with an attenuated total reflectance Fourier transform infrared instrument. The results show that the approach is highly applicable but should only be utilized as an indicative tool. Copyright © 2012 John Wiley & Sons, Ltd.