The loss of MacroH2A1 isoforms in malignant cutaneous melanoma cells has been correlated with poorer prognosis and gain of an increasing malignant potential through the transcriptional upregulation of CDK8 (25); conversely, in uveal melanoma human tissue samples the immunohistochemical overexpression of MacroH2A1 has been observed both in metastasizing primary tumors and liver metastases, suggesting a role of MacroH2A1 as negative prognostic factor and predictor of the risk of disease progression (21). The gene discussed is CDK8; the disease is uveal melanoma.