The reactions of 5-perfluoroalkyl-1,2,4-oxadiazoles 3 with hydroxylamine in DMF give the regioisomeric 3-perfluoroalkyl-1,2,4-oxadiazoles 4 in excellent yields. This process is the first example of ring-degenerate rearrangement (RDR) occurring on five-membered heterocycles by attack of an external bidentate nucleophile, which replaces two heteroatoms of the ring. We suggest that an ANRORC-like mechanism occurs in which the addition of the nucleophilic nitrogen atom (NH2OH) on the C(5) atom of 3 is followed by ring opening and irreversible ring-degenerate closure by attack of the nucleophilic oxygen atom (=NOH) on the C(3) atom of the original ring, realizing an elegant and efficient synthesis of 4 by a C(3)−C(5) annular switch. Ab initio computations on the starting materials and final products, as well as on the proposed intermediates, support the mechanism and shed light on the features of the reaction. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)