The trypanosomatidae family encompasses a group of flagellated protozoans causing a series of severe diseases: Trypanosoma cruzi, Trypanosoma brucei, and species of Leishmania. They have evolved very differently from bacteria, yeast, and animal cells, and have developed unique cellular and genetic pathways. Trypanosomes possess unusually structured mRNAs, identified as a 39-nucleotide spliced leader (SL) and associated cap-4 structure at the mRNA 5' terminus, as products of a special trans-splicing RNA editing mechanism. Counting on the important role of the mRNA 5'-end during eukaryotic translation initiation, the SL sequence and its associated cap-4 structure have been suggested to play a significant part in the recruitment of the ribosome, possibly involving a novel mechanism of initiation. Here, we present a first look at the structure of the T. cruzi 80S ribosome, obtained by cryo-electron microscopy (cryo-EM). Remarkably, the T. cruzi 80S ribosome possesses unusual structural components, in correlation with the secondary structure of its rRNA and the unusually constructed mRNA. In particular, a large helical structure appears in the small subunit, in the vicinity of the mRNA exit channel. We propose that this novel rRNA structure participates in the direct recognition and interaction with the SL sequence and cap-4 structure of the T. cruzi mRNA.