We report on a patient with squamous cell cancer of the left lung who was first considered ineligible for surgery because of severe hypoxemia. A ventilation-perfusion scan showed "reverse" ventilation-perfusion mismatch, with 20% of the total lung perfusion going to the left lung, which showed no ventilation with radioactive aerosols. This pattern suggested that the hypoxemia was due to intrapulmonary functional shunting and could therefore be improved by surgical resection of the tumor. Balloon occlusion of the left pulmonary artery resulted in an immediate rise in PaO2, indicating a right-to-left intrapulmonary shunt. After left pneumonectomy, PaO2 levels were normal. This patient provides an example of dysregulation of the pulmonary hypoxic vasoconstriction response in a non-small cell lung cancer. Lung cancer patients with severe hypoxemia should undergo ventilation-perfusion scanning to look for reverse ventilation-perfusion mismatch suggestive of intrapulmonary functional shunting.