4015 Background: Gastrointestinal poorly differentiated neuroendocrine carcinoma (GI-NEC) are aggressive tumors with Ki-67>20% and usually metastatic at diagnosis. Knowledge about GI-NEC is limited. We retrospectively reviewed clinical data to identify predictive and prognostic markers for advanced GI-NEC patients. Methods: Epidemiological, biochemical, histopathological, treatment and survival data were registered for advanced GI-NEC patients diagnosed during 2000-2009 at 12 Nordic university hospitals. Results: 305 patients were included. Palliative chemotherapy was given to 252 patients, median survival was 11 months. Response rate to 1st-line chemotherapy was 31%, 33% had stable disease. Ki-67<55% was by ROC analyses the best cut-off value concerning correlation to response rate. Response rate to platinum-based chemotherapy was lower in patients with Ki-67<55% (14% vs.44%, p<0.001). Response rate for 84 patients given 2nd-line chemotherapy was 18%, whereas 33% achieved SD. The most important negative prognostic factors for survival were poor performance status, primary colorectal tumors, and elevated baseline platelets or lactate dehydrogenase (LDH) levels. Patients with Ki-67<55% had longer median survival (15 months) than patients with Ki-67>55% (10 months) (p<0.001). Survival and response rates did not differ between the different platinum chemotherapy schedules (cisplatin-based vs. carboplatin-based) or morphology subtypes. 53 patients received best supportive care only with a median survival of 1 month. Conclusions: This is, to our knowledge, the largest study reporting patient and tumor characteristics, treatment and survival in advanced GI-NEC. Performance status, location of primary tumor and blood levels of platelets and LDH were the strongest prognostic factors for survival. Patients with Ki-67<55% had significantly longer survival than patients with higher Ki-67, but were less responsive to platinum-based chemotherapy. Our data indicate that to consider all GI-NEC as one single disease entity may not be correct.