Semiempirical MNDO, AM1, and PM3 calculations are reported for 153 fullerene isomers in an attempt to assess the reliability of these methods through comparisons with ab initio and density functional results. B3LYP/6-31G* relative energies are generally reproduced quite well by these calculations. Qualitative trends in ab initio nucleus-independent chemical shifts at the cage centers are captured by the semiempirical GIAO-MNDO approach while underestimating their absolute values. The agreement between the semiempirical results and the ab initio or density functional reference data is generally better for the larger fullerenes (C60–C102) than for the smaller ones (C20–C50). These systematic comparisons clarify the accuracy that may be expected from semiempirical computations in fullerene chemistry.