The “Critical Assessment of Small Molecule Identification” (CASMI) contest was aimed in testing strategies for small molecule identification that are currently available in the experimental and computational mass spectrometry community. We have applied tandem mass spectral library search to solve Category 2 of the CASMI Challenge 2012 (best identification for high resolution LC/MS data). More than 230,000 tandem mass spectra part of four well established libraries (MassBank, the collection of tandem mass spectra of the “NIST/NIH/EPA Mass Spectral Library 2012”, METLIN, and the ‘Wiley Registry of Tandem Mass Spectral Data, MSforID’) were searched. The sample spectra acquired in positive ion mode were processed. Seven out of 12 challenges did not produce putative positive matches, simply because reference spectra were not available for the compounds searched. This suggests that to some extent the limited coverage of chemical space with high-quality reference spectra is still a problem encountered in tandem mass spectral library search. Solutions were submitted for five challenges. Three compounds were correctly identified (kanamycin A, benzyldiphenylphosphine oxide, and 1-isopropyl-5-methyl-1H-indole-2,3-dione). In the absence of any reference spectrum, a false positive identification was obtained for 1-aminoanthraquinone by matching the corresponding sample spectrum to the structurally related compounds N-phenylphthalimide and 2-aminoanthraquinone. Another false positive result was submitted for 1H-benz[g]indole; for the 1H-benz[g]indole-specific sample spectra provided, carbazole was listed as the best matching compound. In this case, the quality of the available 1H-benz[g]indole-specific reference spectra was found to hamper unequivocal identification.