Pulmonary veno-occlusive disease (PVOD) is a rare disorder that can be misdiagnosed as idiopathic pulmonary arterial hypertension (PAH) and accounts for 5-10% of cases initially considered as idiopathic PAH. PVOD and idiopathic PAH share a similar clinical presentation, genetic background and hemodynamic profile. A definite diagnosis of PVOD necessitates a surgical biopsy, but since it represents a high-risk procedure in these patients, it is contraindicated. Therefore, a noninvasive diagnostic approach using chest high-resolution computed tomography, arterial blood gas analysis, pulmonary function tests and bronchoalveolar lavage is helpful to detect PVOD. PVOD is characterized by a poor prognosis and the possibility of developing severe pulmonary edema with specific PAH therapy. Lung transplantation remains the treatment of choice.