Birt-Hogg-Dubé (BHD) syndrome is a rare inherited genodermatosis characterized by distinctive cutaneous lesions, an increased risk of renal and colonic neoplasia, and the development of pleuropulmonary blebs and cysts. Although the pathology of renal and cutaneous manifestations of BHD has been well described, few reports have detailed the pathologic features of pulmonary involvement. Herein we present the pathologic findings from biopsies of 2 BHD patients with spontaneous pneumothorax: 1 with known BHD and another clinically suspected to have lymphangioleiomyomatosis. Histologic features included basilar cysts comprised of intraparenchymal collections of air surrounded by normal parenchyma or a thin fibrous wall and blebs consisting of collections of air within the pleura. Although these histologic findings are not specific to BHD, their predominantly basilar location contrasts with the apical distribution of other more well-recognized causes of spontaneous pneumothorax, such as emphysematous bullae and idiopathic blebs. It is important for pathologists to be aware of this rare cause of spontaneous pneumothorax because BHD can radiographically simulate other causes of pulmonary cysts and the lung and pleura may be the initial sites of involvement. Patients with BHD are at increased risk for renal neoplasia and may benefit from periodic surveillance. Pathologists should raise the possibility of BHD in nonapical lung biopsies from young or middle-aged patients that show blebs or cysts.