['We postulated that ventilation-perfusion (V/Q) relationships within the lung might influence where lung cancer occurs. To address this hypothesis we evaluated the location of lung adenocarcinoma, by both tumor lobe and superior-inferior regional distribution, and associated variables such as emphysema.', 'One hundred fifty-nine cases of invasive adenocarcinoma and adenocarcinoma with lepidic features were visually evaluated to identify lobar or regional tumor location. Regions were determined by automated division of the lungs into three equal volumes: (upper region, middle region, or lower region). Automated densitometry was used to measure radiographic emphysema.', 'The majority of invasive adenocarcinomas occurred in the upper lobes (69%), with 94% of upper lobe adenocarcinomas occurring in the upper region of the lung. The distribution of adenocarcinoma, when classified as upper or lower lobe, was not different between invasive adenocarcinoma and adenocarcinoma with lepidic features (formerly bronchioloalveolar cell carcinoma, P = 0.08). Regional distribution of tumor was significantly different between invasive adenocarcinoma and adenocarcinoma with lepidic features (P = 0.001). Logistic regression analysis with the outcome of invasive adenocarcinoma histology was used to adjust for confounders. Tumor region continued to be a significant predictor (OR 8.5, P = 0.008, compared to lower region), whereas lobar location of tumor was not (P = 0.09). In stratified analysis, smoking was not associated with region of invasive adenocarcinoma occurrence (P = 0.089). There was no difference in total emphysema scores between invasive adenocarcinoma cases occurring in each of the three regions (P = 0.155). There was also no difference in the distribution of region of adenocarcinoma occurrence between quartiles of emphysema (P = 0.217).'] Is invasive adenocarcinoma of the lung associated with the upper lung regions?