Reduced gene dosage impacting on CDKN2A was predictive of relapse. Loss impacting on P14ARF was, however, more strongly associated with poor prognostic factors such as increased Breslow thickness but particularly with mitotic rate and ulceration, than was loss impacting on CDKN2A. This suggests that loss of P14ARF has a key role in the progression of melanoma. This is consistent with our recent work in metastases, which demonstrated the loss of P14ARF by methylation or deletion to be common in metastases (Freedberg et al.,2008). This is the first study to report on loss across the critical region of 9p in primary melanoma, although loss of CDKN2A coding for CDKN2A has been suggested by others to be associated with poorer prognosis (Cachia et al.,2000; Grafstrom et al.,2005) and loss of CDKN2A expression immunohistochemically correlates with histological invasion (Talve et al.,1997; Pavey et al.,2002). Furthermore, the study suggests that within vertical growth phase melanoma, although loss impacting on CDKN2A was most frequent, wider deletions involving P14ARF and even CDKN2B were associated with poorer histological prognostic factors. Loss of CDKN2A is a common occurrence even in early melanoma (Tran et al.,2002). It is perhaps not surprising then, that further loss of the second melanoma tumor suppressor gene at 9p (P14ARF) impacts on outcome. There is in vitro evidence for a tumor suppressive role for CDKN2B in melanoma (Ha et al.,2008; Peters,2008; Schlegel et al.,2009). That reduced gene dosage impacting on CDKN2B also correlates with poor histological characteristics is supportive of the view that it too may play a role in tumor suppression in melanocytes.