Food safety evaluation of new, genetically modified (GM) plant varieties has led to basic questions regarding the safety assessment of new plant varieties and whole foods derived thereof. An important part of the hazard identification in the European approach is a targeted compositional analysis of new GM plant varieties compared to one or more conventional reference varieties. Comparative analysis will become much more informative with unbiased analytical approaches, such as omics profiling. Analysis tools that estimate the similarity of new varieties to the reference would in turn greatly facilitate hazard identification. Further in-depth biological, functional and eventually toxicological analysis of the data would then only be necessary for varieties that fall outside the scale of those with a history of safe human consumption. For this purpose, the use of a one-class classifier tool was explored in this study to assess and classify transcriptome profiles of potato varieties. Five potato varieties were grown in the Netherlands during the same year (NL samples) and included four biological replicates for four varieties or two biological replicates for the fifth one. They were all analysed in 2011. A sixth variety was grown in the UK in a previous study and a previous year, for which the data are submitted in E-MTAB-605. The two UK samples were analysed in the original study in 2008 and again together with the NL samples in the present study, resulting in four profiles for two samples.