Objective：To study whether normal adult stem cells can have malignant transformation (have tumor characteristics) when exposed to tumor microenvironment. Methods: We established an in vitro model of melanoma cell-induced malignant transformation of epidermal stem cells in a cell co-culture system. The morphological changes of epidermal stem cells were observed before and after induction by phase-contrast microscope; the expression of Ecadherin and P53 mutant protein were examined by immunofluorescence method. Soft agar test was used to examine the colony forming ability of epidermal stem cells after co-culture. Results: Seven days after coculture with A-375 cells, epidermal stem cells began to form visible colonies. The expression of E-cadherin protein was decreased and P53 mutant protein was observed in some cells. Soft agar test showed that 0.55% epidermal stem cells formed colony in the soft agar. Conclusion: This study shows that epidermal stem cells can obtain the characteristics of tumor cells when exposed to inducement of A-375 cells, suggesting that tumor microenvironment can cause disturbance in selfrenewing and differentiation of stem cells.