Hfz5 is a potent cancer associated gene, encoding WNT receptor with the potential to activate beta-catenin - TCF signaling pathway. Here, human Frizzled-5 (FZD5) gene and cDNAs were cloned and characterized. FZD5 was almost identical to Hfz5, except for six amino-acid substitutions at codon 88, 262, 263, 345, 357, and 402. HF5S1 probe (nucleotide position 2036-2535 of FZD5 cDNA) hybridized to 7.5- and 3.5-kb FZD5 mRNAs, and HF5S2 probe (nucleotide position 5572-6194 of FZD5 cDNA) hybridized only to 7.5-kb FZD5 mRNA. FZD5 cDNA was polyadenylated at the nucleotide position 6534, while several FZD5 ESTs were polyadenylated at the nucleotide position 2561. The 7.5- and 3.5-kb FZD5 mRNAs were transcribed probably due to alternative splicing. FZD5 was highly expressed in fetal liver and adult pancreas, and moderately expressed in fetal lung, kidney and adult liver. Among human cancer cell lines, FZD5 was highly expressed in K-562 cells derived from chronic myelogenous leukemia. FZD5 gene, consisting of two exons, was mapped to human chromosome 2q33.3-q34 region, near the FZD7 gene and the FRA2I fragile site. These results suggest that FZD5 up-regulation might play key roles in chronic myelogenous leukemia through activation of the WNT - beta-catenin - TCF signaling pathway.