Animal metal-independent β-galactoside-binding lectins were initially found in vertebrates, but they have recently been isolated from much lower invertebrates, such as nematode and sponge, as well. Further, an eosinophilic lysophospholipase associated with various inflammatory reactions was very recently found to be a new member of this protein family. It appears that β-galactoside-binding lectins and some non-lectin proteins form a superfamily whose members are widely distributed from vertebrates to invertebrates. From the viewpoints of protein architecture, the superfamily members can be subdivided into three types; i.e. ‘proto type’ (the relatively well-studied 14 kDa lectins), ‘chimera type’ (29–35 kDa lectins also known as ε BP/CBP35/Mac2/laminin-binding protein) and ‘tandem-repeat type’ (a newly found nematode 32 kDa lectin). Comparison of their amino acid sequences and mutagenesis studies have suggested the functional importance of some conservative hydrophilic residues (His44, Asn46, Arg48, Glu71 and Arg73 of human 14 kDa lectin). Several non-charged residues (Gly14, Phe45, Pro47, Phe49, Val59, Trp68, Pro78 and Phe79) are also well conserved, and are probably important to maintain the structural framework of these proteins. A consideration of molecular evolution suggests that lectins belonging to this family probably existed in the Precambrian era. Ubiquitous occurrence of these homologous lectins with shared sugar specificity suggests that they are involved in ‘essential minimum’ functions of multicellular animals, possibly in cooperation with their partner glycoconjugates.