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Cancer stem cells expressing CD133 exist in a wide array of tumors and their identification in malignant melanoma may help refine classification, diagnosis and treatment. To study the correlation between CD133 expression in childhood melanoma and lymph node and/or visceral metastasis, we evaluated 12 cases of malignant melanoma and 12 control cases of Spitz nevus occurring in children. Double immunostaining with CD133 and Ki-67 was performed in the cases showing CD133 positivity. Three melanoma patients had lymph node metastasis and only one had multivisceral metastases; CD133 was positive only in these four patients. The Ki-67 index was lower in the CD133 þ cells in comparison with the CD133 À melanoma cells in three cases. We found no positivity for CD133 in all the Spitz nevi. CD133 þ cancer stem cell expression in childhood malignant melanoma might correlate with lymph node and/or visceral metastasis and may have a low proliferative Ki-67 index that might explain their chemoresistance.