A novel method for the topological determination of the relative stability of the C-66 isomers is proposed in this Letter. Among 4478 distinct isomers of the C-66 fullerene, the joint actions of topological compactness (Wiener index) and topological efficiency index correctly sieve the C-66-C-2v molecule detected in Sc-2@C-66 endoclusters. This elegant and fast computational method is suggested to be applicable to any C-n fullerene or graphenic lattice. (C) 2010 Elsevier B. V. All rights reserved.