A comparative genomic analysis of the recently sequenced human body louse unicellular endosymbiont Candidatus Riesia pediculicola with a reduced genome (582 Kb), revealed that it is the only known organism that might have lost all post-transcriptional base and ribose modifications of the tRNA body, retaining only modifications of the anticodon-stem-loop essential for mRNA decoding. Such a minimal tRNA modification set was not observed in other insect symbionts or in parasitic unicellular bacteria, such as Mycoplasma genitalium (580 Kb), that have also evolved by considerably reducing their genomes. This could be an example of a minimal tRNA modification set required for life, a question that has been at the center of the field for many years, especially for understanding the emergence and evolution of the genetic code.