4091 Background: Bone metastasis represents an increasing clinical problem in advanced gastric cancer (GC) as disease-related survival improves. In literature few data on the natural history of bone disease in this malignancy are available. Methods: A retrospective, observational multicenter study aimed to define the natural history of GC patients with bone metastasis was conducted in 22 Italian hospital centres in which these patients received diagnosis and treatment of disease from 1998 to 2011. Data on clinicopathology, skeletal outcomes, skeletal-related events (SREs), and bone-directed therapies for 208 deceased GC patients with evidence of bone metastasis were statistically analyzed. Results: Median time to bone metastasis was 8 months (CI 95%, 6.125–9.875 months) considering all included patients. Median number of SREs/patient was one; less than half of the patients (31%) experienced at least one event and only 4 and 2% experienced at least two and three events, respectively. Median times to first and second SRE were 2 and 4 months, respectively. Median survival was 6 months after bone metastasis diagnosis and 3 months after first SRE. Median survival in patients who did not experience SREs was 5 months. Among patients who received zoledronic acid (ZOL) before the first SRE, median time to its appearance was significantly prolonged compared to control (7 months vs 4 months for control; P:0.0005). Conclusions: To our knowledge, this retrospective analysis is the largest multicenter study to demonstrate that bone metastases from GC are not so rare, are commonly aggressive and result in relatively early onset of SREs in the majority of patients. Furthermore, our large study, which included 90 patients treated with ZOL, showed, for the first time in literature, a significant extension of time to first SRE and increase in the median survival time after diagnosis of bone metastasis.