Pancreatic adenocarcinoma (PC) is the deadliest among common cancers. Because PC progresses rapidly, identifying individuals with a high genetic risk of developing PC is critical to better define emerging strategies for the detection of  early lesions. PC is familial in roughly 10% of patients. Germline mutations in CDKN2A, the major melanoma susceptibility gene, are detected in 30-40% of patients with the melanoma-PC and the familial atypical multiple mole melanoma-PC syndromes, but are considered to play a minor role in familial PC (FPC). Our study identified CDKN2A mutations in 31% of patients with FPC, suggesting that CDKN2A is the main susceptibility gene in Italian FPC families, although melanoma is not a feature of FPC and was not recorded in these patients or their families. The mutation frequency ranged from 20% in FPC families with two affected members to 50% in families with three. Our findings  may be of  value to the purposes of identifying the best candidates for  future PC screening trials in Italy. (By Dr Paola Ghiorzo, http://jmg.bmj.com/content/49/3/164 )