TCF21 is recognized as a candidate tumor suppressor and has been reported to be epigenetically inactivated due to aberrant methylation of the TCF21 gene promoter in a wide range of malignancies, including metastatic melanoma [16], head and neck [17, 18], lung [18–23], gastric [24] and urological cancers [25]. Here, TCF21 is linked to metastatic melanoma.