To discover an active skin depigmenting agent, we isolated a novel inhibitor of melanin biosynthesis from the methanol extract of Erigeron breviscapus using a bioactivity-guided fractionation and identified it as (2Z,8Z)-matricaria acid methyl ester by means of spectroscopic analysis. The compound showed strong whitening activity in melan-a cell. Compared with arbutin (IC(50)=4.0 mM) as a positive control, the depigmentation IC(50) value for (2Z,8Z)-matricaria acid methyl ester was 25.4 muM in B16F10 melanoma cell. Moreover, its inhibitory effect on tyrosinase, the key enzyme of melanogenesis, was examined by in vivo and in vitro tyrosinase assay and Western blot. The results indicate that (2Z,8Z)-matricaria acid methyl ester isolated from Erigeron breviscapus is a promising compound that could be useful for treating hyper-pigmentation as skin-whitening agents.