Transfer RNAs (tRNAs) are ancient molecules likely predating the translation machinery. These extremely conserved RNA molecules transfer amino acids to the ribosome for the synthesis of proteins encoded by mRNAs, but canonical tRNAs are not protein-coding RNAs. Surprisely, when virtually translated, I observed that peptides derived from tRNA sequences match thousands of protein entries in databases. The analysis of these sequences indicates that the vast majority of these tRNA-derived proteins are annotated as small hypothetical peptides, likely arising from sequencing, prediction and/or annotation errors. But life often surpasses fiction. Importantly, tRNA-encoded amino acid domains were also found embedded in large functional proteins. Phylogenetic analysis of representative tRNA-derived protein domains may provide new insights into the origin, plasticity, and evolution of protein-coding genes.