The genetic code can be read by cognate but also near cognate tRNAs. This flexibility is assumed to be conferred mainly by a mismatch between the third base of the codon and the first of the anticodon (so called wobble position). However this simplistic explanation often underestimates the importance of nucleotide modifications in the decoding process. Taking advantage of a system where only near cognate tRNA can decode a specific codon, we addressed the role of six modifications found in the anticodon, or adjacent nucleotides, of tRNA Tyr, Gln, Lys, Trp, Cys and Arg in Saccharomyces cerevisiae. We show that almost systematically, the modification confers to these tRNAs the ability to act as a near cognate tRNAs on stop codons, without noticeable impact on their ability to decode cognate or near-cognate sense codons. These findings reveal an important role of modifications for tRNA decoding.