Humans are widely exposed to environmental chemical toxicants potentially related to disease susceptibility. Polybrominated diphenyl ethers (PBDEs) present a proven risk associated with cancer, but no studies are related with the tumor progression. The decabromodiphenyl ether (BDE-209) is a flame-retardant detected in human plasma, breast milk and umbilical cord. Melanoma is a skin cancer with high metastatic potential and poor response to therapies. The use of alkylating agents such as dacarbazine is still a common protocol for the treatment of melanoma, mainly in Brazilian Public Health Care System. Recently, we reported the role of BDE-209 on the incidence of melanoma metastasis in different organs of mice after inoculation of B16-F10 cells. In the current study, we describe the effects of BDE-209 on dacarbazine treatment for melanoma. Adult male and female C57BL6 mice were exposed to BDE-209 for 45 days, inoculated with B16-F10 cells and treated with dacarbazine for 21 days (five doses of 40 mg.kg− 1). At 66th day, the animals were euthanized, and the blood, lung, liver, kidney and brain were sampled for hematological, biochemical and metastasis counting analyses. The results showed a decrease of lung metastases in animals treated with dacarbazine and a significant increase in mice previously exposed to BDE-209. Foremost, BDE-209 impaired dacarbazine treatment. These findings demonstrate the effect of BDE-209 and the decreased efficacy of dacarbazine treatment, favoring cancer progression and affecting the disease prognosis.