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Incidence rates for laryngeal cancer in Central Europe are among the highest in the world. The authors recruited cases and controls between 2000 and 2002 for the Central and Eastern Europe Multicenter Study to investigate the role of tobacco and alcohol as causes of laryngeal cancer in this region. A total of 384 incident squamous cell cases were included, comprising 254 glottic and 108 supraglottic cancers. Hospital controls were chosen from within the same catchment area, from diseases unrelated to tobacco or alcohol (n = 918). Significant dose-response trends for frequency and duration of tobacco use were observed for both supraglottic and glottic cancers, with potentially a more important effect for supraglottic cancer. Quitting smoking was protective against laryngeal cancers after 5 years. Any increases in risk for alcohol drinking were generally moderate and nonsignificant. A greater than multiplicative interaction was observed between tobacco and alcohol on the risk of laryngeal cancer (p = 0.04). Approximately 87% of laryngeal cancer cases in Central Europe are attributable to tobacco use, of which 75% and 12% are due to current and past smoking, respectively. Approximately 39% are attributable to the interaction between alcohol and tobacco. Preventive efforts to encourage current smokers to quit are likely to be the most effective way to reduce the incidence of laryngeal cancer in this region.