Rationale:Birt-Hogg-Dubé (BHD) syndrome is a rare autosomal recessive genetic disorder caused mainly by mutations in the tumor suppressorFLCNgene. Tumors caused byFLCNmutations are frequently benign and develop in skin, lungs, kidney, and other organs, leading to a variety of phenotypes that make early diagnoses of BHD challenging.Patient concerns:A 51-year-old female was admitted to Shanghai Seventh People Hospital due to chest congestion and dyspnea that had persisted for 3 years and aggravated for 1 month. She had been diagnosed with pneumothorax prior to this submission, but the etiology was unknown.Diagnoses:Chest computed tomography (CT) revealed multiple pulmonary cysts and pneumothorax, and her family members shared similar manifestation. Whole-exome sequencing analysis indicated a heterozygousFLCNsplicing mutation (c.1432 + 1G > A; rs755959303), which was a pathogenic variant indicated in ClinVar. Based onFLCNmutation and the family history of pulmonary cysts and pneumothorax, BHD syndrome was finally diagnosed, which had been delayed for 3 years since her first pneumothorax.Interventions:Pulmonary bullectomy and pleurodesis were finally conducted due to the poor effects of thoracic close drainage.Outcomes:Her pneumothorax was resolved, and no recurrence was found in 2 years.Lessons:Our study highlights the importance of genetic analysis in diagnosis and clinical management of BHD syndrome.