Epigenetic regulation of tumor suppressor genes provides an attractive mechanism for tumors in which mutations and structural changes are rare. The latter may apply to uveal melanoma for which little is known of the genes that contribute to tumor development. In the search for genes, uveal melanoma is often compared to its counterpart in the skin, cutaneous melanoma. One of the major cuteneous melanoma genes is the p16 encoding CDKN2A gene for which mutations and deletions are the major mechanisms of inactivation. Deletions and mutations in CDKN2A are however rare in uveal melanoma; still p16 expression is lacking in half of the cell lines. Using methylation analysis and methylation inhibition in cell culture, we have shown that the underlying mechanism of loss of p16 expression in these cell lines is methylation of CDKN2A. This observation is not disputed but controversy arises when primary tumors are analyzed and estimates are given for the extend of CDKN2A methylation in uveal melanoma[2-4]. The study by Moulin et al is an example of a study that displays some remarkable deviations from results we and others have achieved previously[5,6]. We would like to comment on some of the technical and biological factors that may contribute to the lack of consistency in the results that are achieved in the field of uveal melanoma epigenetics.