A mannose-specific lectin with agglutination activity against a yeast, Saccharomyces serevisiae, was purified from conger eel (Conger myriaster) skin mucus. The lectin, named conCL-s, has a tetrameric structure consisting of two non-covalently associated dimers whose constituent monomers with a molecular mass of about 16,000 Da are linked by a disulphide bond. conCL-s is composed of 173 amino acid residues including a 24-residue signal peptide, and belongs to the C-type lectin family, which is typically characterized by binding to sugar in a Ca2+-dependent manner. Nevertheless, conCL-s showed Ca2+-independent activity in its yeast-binding. The gene expression of the lectin was widely detected in external and internal mucosal tissues, i.e., skin, gills, tongue, buccal cavity wall and esophagus. In these tissues, mRNA of conCL-s was exclusively distributed in club cells, which are one of the major components of the epidermis and mucosal epithelium in Anguilliforme species. conCL-s showed agglutination activity to a bacterium, Escherichia coli. Furthermore, attachment of the lectin to microspheres significantly enhanced their phagocytosis in conger eel macrophages. These findings suggest that conCL-s acts as an opsonin and plays an important role in the innate immunity on the body surface in conger eels.