250 Background: Pancreatic cancer is the deadliest solid cancer and currently the fourth most frequent cause of cancer-related deaths. Many studies have demonstrated that pancreatic cancer is a group of heterougeneous disease with different therapeutical implications and prognosis. Aim of our analysis was to analyze the HER-family status in pancreatic cancer. Methods: We immunohistochemically assessed surgical specimens and macrobiopses for several biological targets. K-ras, HER-1, HER-2 and HER-3 were analyzed. Results: 62 specimens were analyzed in our centre. 30 samples were K-ras wild-type, 70% of these were EGFR positive. While 32 samples have a mutant form of K-ras, 87.5% were EGFR positive. HER-2 resulted negative in all specimens. In the K-ras wild-type group, 17% have high expression of HER-3, 20% a low one; in mutant K-ras group 16% are high expressing while 34% have a low HER-3. Conclusions: Over the past decades, there has hardly been any substantial therapeutic progress regarding clinical endpoints in pancreatic cancer, thus in the era of target therapies the molecular biological classification of these neoplasms have an ever more important role for developing tailored therapies. Our analysis show a low rate of k-ras mutations (52%) and seems to suggest that anti-EGFR strategies may represent an interesting treatment option in pancreatic cancer as long as a preliminary molecular selection is applied. Numerous international trials are evaluating the role of new drugs targeting HER-2 in association with chemotherapy in metastatic pancreatic cancer. On the contrary, our data suggest that HER-2 directed therapies are not likely to represent a relevant choice in this setting.