Objective: OCT4, as a transcription factor has a role in stemness maintenance and assumed to be a self-renewal regulator in different kind stem cells including cancer stem cells. It has two spliced variants, OCT4A and OCT4B. Oct4A regulate self-renewal and pluripotency in stem cells, while the function of Oct4B is unknown. The aim of this study is assessment of OCT4A and OCT4B expression in melanoma stem cells. Materials and Methods: D10 melanoma cell line was grown in complete RPMI medium. The cells were sorted due to the expression of CD133 cell surface marker-one of the most important cancer stem cell (CSC) marker in solid tumors- named CD133+ and CD133- population. Afterward, the expression of OCT4A and OCT4B were assessed in unsorted, CD133+ and CD133- population with specific primers. The paired two-tailed Student's t test was used to compare groups and P value less than 0.05 was considered statistically significant. Results: Our results revealed that OCT4B variant wasn’t differentially expressed between populations. While OCT4A expression in CD133+ (cancer stem cells) population was significantly more than unfractioned and CD133- population (1.8 fold). Conclusion: According to this result OCT4A can a candidate for cancer stem cell population and targeting of this factor in cancer stem cells maybe inhibited self-renewal and pluripotency.