Histidine decarboxylase (HDC) is expressed by the cells of melanoma, in which the histamine content tends to be relatively high. This study shows that elevated expression of HDC was found by western blot analysis of primary and metastatic melanoma tissue using a polyclonal HDC specific antibody. The specificity of anti-HDC antibody was confirmed by inhibition of HDC translation (i.e., immunopositivity) in melanoma cells by HDC-specific antisense oligonucleotide. Moreover, the decrease in proliferation caused by HDC antisense oligonucleotides indicates considerable functional relevance of histamine synthesis in melanoma growth and suggests a possible in situ application of specific antisense oligonucleotides for HDC in melanoma therapy.