The findings of our study, summarized herein, demonstrate that DDX11 is expressed at high levels in primary and metastatic melanomas, but not in melanocytes of normal skin, atypical nevi, or melanoma in situ, and that suppressing DDX11 expression in advanced melanomas leads to severe defects in chromosome segregation, and with potential relevance to therapeutic intervention, inhibition of melanoma cell proliferation and rapid melanoma cell death. Here, DDX11 is linked to in situ carcinoma.