e20566 Background: Residential radon is the second most important risk factor for lung cancer. We aim to asses the effect of residential radon exposure on the risk of SCLC in general population. Methods: A multicentric hospital-based case-control study was designed including 10 hospitals from Spain and Portugal. Incident cases with pathological diagnosis of SCLC were prospectively recruited. Controls consisted in patients undergoing non-complex surgery unrelated to tobacco consumption. All study participants were sent a radon detector. Results: A total of 375 cases and 902 controls were recruited. 24.5% of cases were women. The median age at diagnosis was 66 for cases. 6.4% of the cases were younger than 50 years. Tobacco consumption was higher in cases compared to controls. Residential radon concentrations were higher than 147 Bq/m3 in 161 SCLC cases (42.9%). Median residential radon concentration was also higher in SCLC cases compared to controls (152.5 Bq/m3 vs 142 Bq/m3). Those people exposed to more than 147 Bq/m3 and heavy smokers showed an OR of 72,62 (95%CI 17.95 - 499.41) compared to never-smokers with less than 50 Bq/m3. Conclusions: radon exposure seems to increase the risk of small cell lung cancer. There is a significant lung cancer risk departing from 148 Bq/m3 and there is also a linear dose-response pattern. Tobacco consumption may also produce an important effect modification for radon exposure. Those individuals exposed to high radon concentrations and heavy smokers can have a very high risk of this cancer type compared with their low exposed and never-smoking counterparts. It is necessary to increase radon awareness among citizens and administrations in order they can establish the necessary protective and mitigation measures against residential radon. Effect modification between residential radon exposure and tobacco consumption on the risk of small cell lung cancer.[Table: see text]