Malignant pleural effusion is a common cause of morbidity and mortality in patients suffering from end-stage metastatic cancer. Malignant pleural effusion is associated with a shortened survival of 3 to 12 months after diagnosis, with 1- and 6-month mortality rates of 54% and 85%, respectively. Nearly all medical management in these patients is directed toward palliation of symptoms caused by pleural fluid accumulation. Options for treatment are repeated thoracentesis, use of chronic indwelling catheters, pleurodesis, and pleuroperitoneal shunts. Associated procedure risks include infection, bleeding, pneumothorax, and respiratory failure. Transthoracic ultrasound use is advocated to minimize procedural risks for thoracentesis and indwelling pleural catheter (IPC) placement. Most patients with advanced metastatic cancer and pleural effusion are not suitable candidates for pleuroscopy-delivered pleurodesis. Therefore, IPC is more commonly chosen to palliate respiratory symptoms related to pleural fluid accumulation from pleural tumor burden. Although pleural catheter complications are low, malignant seeding of the pleural tract can occur. Transthoracic ultrasound use to determine the presence of pleural tract seeding in conjunction with guided percutaneous biopsy has not been described. We report the use of ultrasound-guided percutaneous biopsy to diagnose metastatic seeding of an IPC.