OBJECTIVE Unilateral hyperlucent lung on chest radiograph is uncommon in children. It is often found incidentally and always refers to Swyer-James syndrome, with decrease in pulmonary vascularity and air trapping during expiration. However, it may occasionally mimic other serious lung diseases such as pulmonary hypoplasia/aplasia, defect of pulmonary artery, and other primary pulmonary disorders. In this study, we hypothesized that there would be characteristic patterns in pulmonary ventilation and perfusion scintigraphy (V/Q scan) in children with unilateral hyperlucency on chest film, which could play an important role in differential diagnosis of this disease group explicitly. METHODS Children with unilateral hyperlucency on chest radiograph had a detailed clinical examination and underwent echocardiography, chest computed tomography, selective pulmonary angiogram, flexible bronchoscopy, and pulmonary V/Q scan. RESULTS A total of 10 cases were enrolled, including two cases of unilateral pulmonary artery agenesis, three cases of Swyer-James syndrome, two cases of agenesis of the right lung, one case of lobar emphysema, and two cases of tetralogy of fallot with left pulmonary artery stenosis. Besides, an overview of children with unilateral hyperlucent lung is provided, reviewing nine studies (171 patients), including our clinical experience, and finally an algorithm for diagnosis unilateral hyperlucent lung is proposed, based on the characteristics of V/Q scan. CONCLUSIONS We chose a descriptive approach to the V/Q scan in children with unilateral hyperlucent lung on chest radiograph. This result enables us to promote the V/Q scan as a first-line tool in evaluating these patients and to avoid further unnecessary procedures.