Cutaneous melanoma (CM) is an aggressive skin cancer, more prevalent in Australia. BRAF inhibitors (BRAF-i) are the standard of care for BRAF-mutant CM, which account for ~50% CM. However, drug resistance develops rapidly in these patients. The presence of primary resistant subclones within the tumour facilitates the emergence of acquired resistance, leading to treatment failure. Thus, understanding the mechanisms underlying intrinsic resistance is critical to devise new therapeutic strategies to obtain long-term disease control. ATP-binding cassette B5 (ABCB5) transporters are reported to efflux anti-cancer drugs from CM cells and mediate resistance. The active efflux mechanism of ABCB5 transporters cause decreased drug accumulation within tumour cells, leading to tumour cell survival. However, the role of ABCB5 transporter in the efflux of BRAF-i have not been investigated. In this study, we examined the intrinsic expression of ABCB5 gene in BRAF-mutant CM cells. Five out of seven BRAF-mutant CM cell lines intrinsically express ABCB5. These five CM cell lines showed increased ABCB5 expression when treated with BRAF-i (short-term), quantified by qRT-PCR and flow cytometry. However, the level of ABCB5 expression varied between the cell lines. Previous report have implicated ABC transporter upregulation as an early event in the development of resistance. This indicates that BRAF-i might possibly act as substrates for ABCB5 transporters and be effluxed from tumour cells. Further, expression of some known markers of resistance such as PMEL, CSPG4, MLANA, MITF, ABCB5, AXL, PAX3, KDM5B, SOX10 and NGFR were investigated in BRAF-i treated cells by qRT-PCR, to investigate any association with other markers of resistance. Interestingly, increased ABCB5 gene expression was accompanied by increased pigmented state associated genes such as MITF, MLANA, PMEL and decreased AXL and NGFR expression. Similar results were observed in single cell RNA-seq analysis from previous studies performed on tumour cells derived from CM patients. These results together indicate a possible association between pigmented state associated genes and ABCB5. Further studies are required to confirm these results.