In the course of screening a human hepatoma cDNA library with antibody raised against a mammalian lectin with subunit molecular weight of about 14,000, we detected a partial cDNA encoding a related but distinct protein that was possibly a homologous lectin (Gitt and Barondes, 1986). We here report the isolation and sequencing of a full-length cDNA for this protein from a HepG2 cDNA library. The cDNA encodes a protein with subunit molecular weight of 14,650. Expression of the coding sequence in Escherichia coli yields a product that binds to a lactose affinity column and is specifically eluted with lactose, confirming that this new protein is a lectin. Like its well studied relative, here called L-14-I, the new lectin, L-14-II, exists as a homodimer in solution. The two related human lectins have 43% amino acid sequence identity. The genomic DNA encoding L-14-II (LGALS2) contains four exons with similar intron placement to L-14-I (LGALS1); but the genomic upstream region, which contains several sequences characteristic of regulatory elements, differs significantly from L-14-I.