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Bronchoscopy is a common and safe procedure with low mortality rates and complications. The risk of pneumothorax (PTX) post bronchoscopy is estimated to be 0.1% but increases to 1-6% with the addition of transbronchial lung biopsy (TBB) to the procedure. Studies have shown that a short observation period is adequate after TBB, and the usual practice is to perform a portable chest radiograph (CXR) to rule out PTX. Delayed PTX is a rare complication post-TBB and very few cases have been reported in the literature. In this report, we discuss a patient with delayed PTX 48 hours post-TBB. A 71-year-old male with a history of malignancy of unknown primary with metastasis to the sacrum and vertebral column presented with lower limb weakness status post-palliative radiation to the spine. His sacral lesion biopsy was inconclusive. He was currently on oral steroids. He was noted to have a left upper lobe lung nodule on a CT scan of the chest. He underwent bronchoscopy with TBB to determine if it was a primary lung malignancy. He was stable post-procedure with an unremarkable CXR for PTX and was discharged with outpatient follow-up. Two days later, he presented to the emergency department with shortness of breath and hypoxemia. A CXR was performed, which showed a left-sided PTX. A chest tube was placed, and a follow-up CXR showed lung immediate re-expansion. The chest tube was removed after two days and the patient was discharged home after a total of four days of hospitalization. Iatrogenic PTX can be due to diagnostic and/or therapeutic interventions. PTX after procedures can be classified as acute (one to four hours post-procedure) or delayed (>4 hours post-procedure). It is recommended to have a CXR within an hour post-TBB. To our knowledge, very few cases of delayed PTX post-TBB have been reported, mostly among lung transplant patients and those with chronic infections such as tuberculosis. In prior reports, it has been speculated that a visceral pleural defect might occur during a biopsy, but is protected by blood clot formation in the proximal bronchus. A PTX then occurs after fibrinolysis of the blood clot. Low immunity and poor wound healing due to chronic inflammation or steroid use can play a role in causing a delayed PTX. Also, the use of pain drugs such as opioids is associated with iatrogenic PTX. Patients with underlying lung disease such as emphysema are more prone to developing a PTX. Another hypothesis is that a tissue flap is created after the biopsy, which obstructs the airflow during exhalation, thereby resulting in a PTX. On the other hand, it is known that lung malignancies, either primary or metastatic, can increase the risk of secondary PTX. In our case, the temporal relationship of the delayed PTX with bronchoscopy makes it more likely that it was related to the lung biopsy (in our case, poorly differentiated non-small cell carcinoma). The underlying malignancy with low immunity, chronic tissue inflammation, and current steroid use may have resulted in delayed lung healing at the biopsy site. This case report highlights the importance of considering delayed PTX among high-risk patients who undergo such procedures. Delayed PTX is a rare complication post-TBB and should be considered in patients who are stable post-procedure but present with dyspnea and/or hypoxemia even days after the procedure.