Tilapias are a group of cichlid fish that are of world-wide importance for aquaculture. The genome of the Nile tilapia (Oreochromis niloticus)has recently been sequenced and protein-coding genes have been predicted using high-throughput algorithms. We were interested in evaluating how well the predicted theoretical proteome of O. niloticus matches to actually expressed proteins in a congeneric species, the Mozambique tilapia (O. mossambicus). Moreover, we also asked what Gene Ontology (GO) categories were represented in the expressed proteome of various tissues including gill epithelium, brain, and kidney. GO categories were assigned to computationally predicted O. niloticus proteins using BLAST2GO and the experimental proteomes of the various O. mossambicus tissues compared against this template. Our results show that 500 proteins can be identified in each tissue using online LCMS-based proteomics with high confidence in O. mossambicus when using the O. niloticus proteome as a reference(FDR < 2%). Moreover, we found that the expressed proteomes have tissue-specific signatures that are represented by corresponding GO categories. Supported by NSF grant IOS-1049780.