Middle lobe syndrome (MLS) is an uncommon lung disorder involving the right middle lobe and/or lingula and is characterized by a spectrum of clinical and pathological lesions ranging from recurrent atelectasis or pneumonias to bronchiectasis. Despite several series reporting the clinical features of MLS, histopathological descriptions are rare. We reviewed the clinical characteristics and pathological findings in 21 patients with MLS who underwent surgical resections. Six male and 15 female patients between the ages of 5 and 80 years (mean, 47 years) were studied. All patients were symptomatic and complained of chronic cough (8), hemoptysis (6), chest pain (4), dyspnea (3), or fever (2). The right middle lobe was involved in 11 patients, the lingula in four patients, and both right middle lobe and lingula in six patients. Chest radiographs, bronchograms, and/or computed tomography scans were available for review in 19 patients and showed consolidation (8), bronchiectasis (9), patchy infiltrates (5), and atelectasis (4) in various combinations. Pathological findings included bronchiectasis in 10 patients, chronic bronchitis/bronchiolitis with lymphoid hyperplasia in seven, patchy organizing pneumonia in six, atelectasis in five, granulomatous inflammation in five, and abscess formation in four. Three patients with granulomatous inflammation had associated atypical mycobacterial infection. Broncholithiasis was confirmed by pathological examination in one patient. No pathological cause for bronchial obstruction was identified in the remaining 20 patients, although one was thought to have had broncholithiasis on the basis of preoperative bronchoscopy. The presence of bronchiectasis, bronchitis or bronchiolitis, organizing pneumonia, or atelectasis in specimens from the right middle lobe or of lingula in the absence of an identifiable cause of bronchial obstruction should suggest a diagnosis of MLS.