Circulating tumor cells (CTCs) are cancer cells shed from either a primary tumor or its metastases that circulate in the peripheral blood. CTCs are potential seeds for metastases, and analyses of CTCs may allow earlier detection of metastasis-capable malignancy, monitoring for tumor recurrence, and accurate prognostication. Studies on CTCs have focused mainly on the detection of epithelial cancer cells. In this issue, De Giorgi et al. show that CTCs can be detected in melanoma patients using a filtration method, and that a higher percentage of patients with metastatic melanoma have detectable CTCs than do patients with primary melanoma.