Background: The magnitude of the link between cigarette smoking and lung cancer may vary by histological type. Methods: We used polytomous logistic regression to evaluate whether aspects of smoking have different effects across four histological types in the Nurses' Health Study. Results: From 1976 to 2002, we identified 1062 cases of lung cancer: squamous cell (n = 201), small cell (n = 236), adenocarcinoma (n = 543) and large cell carcinoma (n = 82), among 65 560 current or former smokers. Risk reduction after quitting ranged from an 8% reduction (relative risk (RR): 0.92, 95% CI 0.91 to 0.94) to a 17% reduction (RR: 0.83, 95% CI 0.80 to 0.86) per year for adenocarcinoma and small cell carcinoma, respectively, with a 9% reduction observed for large cell carcinoma and an 11% reduction observed for squamous cell carcinoma. The association of age at smoking initiation and former cigarette smoking was similar across types, while the association of smoking duration differed. The risk of adenocarcinoma increased by 6% per year of smoking, compared to 7% for large cell, 10% for squamous cell and 12% for small cell. The 6% difference between adenocarcinoma and small cell carcinoma is equivalent to a 3.2 to 9.7-fold increase in risk for 20 years of smoking. Conclusions: The effects of the number of cigarettes smoked per day and years since quitting smoking are different across the major types of lung cancer, which are fully appreciated at long durations of smoking and smoking cessation. Smoking prevention and cessation should continue to be the focus of public health efforts to reduce lung cancer incidence and mortality.