Regarding a patient with dyspnea, the history and physical examination often lead to the correct diagnosis. In some circumstances, when more than one underlying disease is present, the diagnostic process can be more challenging. We describe an unusual case of dyspnea and persistent hypoxemia related to a hepatopulmonary syndrome in a 53-year-old patient with known heart failure and chronic liver disease. Initially managed with intravenous diuretic therapy, due to signs of lung and peripheral congestion, our patient did not improve as expected; therefore we performed more advanced studies with a chest-abdomen CT scan and a right heart catheterization. They showed, respectively, no signs of parenchymal and vasculature lung disease, a cirrhotic liver disease, splenomegaly, signs of portal hypertension, and high cardiac output with normal pulmonary vascular resistance. These results, along with the association of hypoxemia and chronic liver disease, suggested a hepatopulmonary syndrome. The diagnosis was confirmed by the demonstration of an intrapulmonary vascular dilatation with right to left shunt during a microbubble transthoracic echocardiography and a lung perfusion scan. Liver transplantation is the only successful treatment for this syndrome; however, the patient became soon unsuitable for this strategy, due to a rapid clinical deterioration.