Cytologic examination of specimens obtained from the respiratory tract is a lung cancer diagnostic procedure with high specificity but moderate sensitivity. The use of molecular biomarkers may enhance the sensitivity of cytologic examination in the detection of lung cancer. Complement factor H, a protein secreted by lung cancer cells, was quantified in a series of bronchoalveolar lavage supernatants from lung cancer patients and patients with nonmalignant respiratory diseases. Albumin, total protein content, and hemoglobin were also analyzed. Results were validated in independent sets of bronchoalveolar lavage and sputum supernatants. There was a significantly higher concentration of factor H in bronchoalveolar lavage samples from lung cancer patients. The sensitivity and specificity of the factor H test was 82% and 77%, respectively. These results were validated in an independent set of patients with nearly identical results. Furthermore, 70% and 45% of bronchoalveolar lavage fluids from central and peripheral tumors, respectively, reported as cytologically negative, were classified as positive using this marker. Finally, the test was evaluated in a series of sputum supernatants from lung cancer patients and controls. The sensitivity and specificity of the factor H test in this series was 80% and 88%, respectively. Factor H is elevated in bronchoalveolar lavage and sputum from lung cancer patients. Measurement of molecular biomarkers, such as complement factor H, may be used in the future as an adjunct to cytology in the diagnosis of malignant pulmonary diseases.