This study provides the first investigation of the diversity, structure, and molecular evolution of MHII β genes in a non-model percid species – the Eurasian perch (Perca fluviatilis L.). PCR primers developed here were highly specific, and documented a high diversity of the MHII β1 domain in perch. Our results suggest a minimum of eight MHII β loci in this species – a finding congruent with several studies suggesting that many Euteleostei posses multiple MHII β loci. As for other vertebrates, both positive selection and gene-conversion contribute to the reported high allelic diversity. Similarly, the MHII β1 domain in perch exhibits a characteristic MHC fold known from other vertebrates. In addition, our results suggest some teleost specific differences of the MHII β1 domain, including: differences in chemical properties of specific amino acids in the β1 domain, the absence of the tetrapod specific glycolisation signal, and differences in the positions of some of the positively selected codons in the MHII β1 domain, which are presumably involved in antigen binding. Future studies should investigate the teleost MHII β genes in more details in order to confirm the suggested differences, and to determine the extent to which these differences prevail in different teleost lineages.