97 Background: Surgery is the only potentially curative treatment for LAGC. Evidences suggest that perioperative CT (pCT) plus surgery is superior to surgery alone, whereas studies on adjuvant CT (aCT) are controversial. Guidelines recommend a pCT approach in pts with stage II/III, nevertheless in real-life many pts receive immediate surgery followed by aCT. Histology influences both survival and pathological response with worse prognosis among diffuse LAGC. No trial has compared pCT and aCT or investigated the impact of histology on the outcome of these different approaches. We hypothesized that histology may predict a different benefit from CT administered in the two settings, allowing to define the optimal strategy. We performed a study comparing the two approaches according to histology. Methods: We retrospectively analyzed pts with stage II/III LAGCs treated at our Institution between Jan-09 and Jan-17. The objective of the study was to evaluate the impact of histology (intestinal and diffuse) on survival according to strategy approach (pCT vs aCT). Primary endpoints were DFS and OS. Results: 81 pts had diffuse LAGC (29 received pCT, 52 aCT) and 60 had intestinal LAGC (32 received pCT, 29 aCT). In the intestinal cohort both DFS and OS were significantly higher in pts treated with pCT compared to aCT (DFS: HR 0.3, p = 0.02; OS: HR 0.3, p = 0.03). On the contrary in the diffuse cohort both DFS and OS were significantly lower in pts receiving pCT compared to those receiving aCT (DFS: HR 2.4, p = 0.0014; OS: HR 2.6, p = 0.0012). Conclusions: Our study, although retrospective and small-sized, shows that the survival benefit of pCT is limited to intestinal LAGC, whereas in diffuse LAGC the administration of pCT appears detrimental. Indeed, diffuse LAGC is known to be chemoresistant and pCT might delay surgery allowing metastasization. Despite the arising of recent molecular classification, still far from modifying clinical practice, histotype might represent an easy factor to discriminate pts benefitting from pCT (intestinal) to those in whom upfront surgery might be recommended (diffuse). Our hypothesis needs to be confirmed in prospective trials.