Several methods have been developed for the analysis of substituted pyrazines and related substances in potato chips. Following separation/detection approaches (all employing head-space solid phase microextraction, HS-SPME, for volatiles sampling), have been critically assessed in our study: (i) gas chromatography-ion trap mass spectrometry (GC-ITMS), (ii) gas chromatography-time-of-flight mass spectrometry (GC-TOFMS); (iii) comprehensive two-dimensional gas chromatography-time-of-flight mass spectrometry (GC x GC-TOFMS). Although in none of the tested systems full chromatographic resolution of some isomeric pairs could be achieved, the use of GC x GC-TOFMS offered the best solution, mainly because of distinctly lower limits of quantification (LOQs) for all of 13 target alkylpyrazines. In addition to good performance characteristics, a non-target screening and tentative identification of altogether 46 N-containing heterocyclic compounds (pyrazines, pyrrols, pyridines, pyrrolidinones, and tetrahydropyridines) was also enabled.