The complement regulatory protein (CRP) of Trypanosoma cruzi is a surface glycoprotein that confers to the infectious trypomastigote forms a protection against the lytic activity of the host complement. To define better the CRP within the large family of trans-sialidase-like proteins, we investigated the CRP sequence diversity in the trypomastigote stage of several T. cruzi strains and used a phylogenetic analysis based on the amino acid alignment of the CRP with the 200 top scoring proteins detected through a database sequence homology search. Intrastrain variations revealed the presence of several different CRP transcripts per strain and the interstrain variability was consistent with the subdivision of T. cruzi into genetic lineages. The phylogenetic analysis including the putative proteins retrieved from the T. cruzi genome project database did not differentiate the CRP from the FL-160 proteins and clustered them into a monophyletic group characterized by the presence of the 12 amino acid mimicry epitope that shows cross-reactivity with nervous tissues. In turn, proteins of this group did not bear classical complement control protein modules involved in C3b/C4b binding. The high sequence similarity observed in this group of CRP-like proteins opens up new prospects for the exploration of their functional diversity or similarity and their involvement in the resistance to the complement. This study provides information for the T. cruzi genome annotation of the trans-sialidase-like putative proteins