Marfan syndrome is one of the most common connective tissue diseases and may manifest with a range of symptoms and pathologic changes. We present a retrospective series of 5 cases of patients with Marfan syndrome and pulmonary pathology. Patients were young to middle-aged adults with absent or minimal smoking histories and absent to severe clinical pulmonary symptoms. Tissue specimens were obtained from the surgical pathology and autopsy services. Histologic examination revealed a consistent pattern of distal acinar emphysema in all patients. Comparisons are made with other cystic-type diseases of the lung that may histologically mimic this pattern. This is the largest contemporary series of histologic pulmonary involvement of Marfan syndrome and the first to describe this pattern of pulmonary changes in this patient population.