STUDY OBJECTIVES: To clarify the possibility of a hereditary predisposition to lung cancer, we investigated the association between a family history of lung cancer and subsequent risk of lung cancer in a large-scale, population-based cohort study. DESIGN: We investigated 102,255 middle-aged and older Japanese subjects (48,834 men and 53,421 women) with 13-year follow-up. A total of 791 cases of lung cancer were newly diagnosed during the follow-up period. RESULTS: A family history of lung cancer in a first-degree relative was associated with a significantly increased risk of lung cancer (hazard ratio [HR], 1.95; 95% confidence interval [CI], 1.31 to 2.88). The association was stronger in women than in men (HR, 2.65; 95% CI, 1.40 to 5.01 and HR, 1.69; 95% CI, 1.03 to 2.78, respectively), and in never-smokers than in current smokers (HR, 2.48; 95% CI, 1.27 to 4.84 and HR, 1.73; 95% CI, 0.99 to 3.00, respectively). In addition, family history was more strongly associated with the risk of squamous cell carcinoma than with other histologic types (HR, 2.79; 95% CI, 1.37 to 5.68), while no clear increase in risk was observed in adenocarcinoma and small cell carcinoma. A family history of overall cancer was not associated with an increased risk of lung cancer. CONCLUSIONS: These results suggest that those with a family history of lung cancer are more likely to acquire lung cancer themselves.