A 55-year-old woman with a prior 15-pack-year smoking history presented with persistent cough and minor weight loss. Chest imaging revealed two masses in the right upper lobe, mediastinal adenopathy, a right-sided pleural effusion, and pleural nodules. Video-assisted pleuroscopy identified lung adenocarcinoma in the pleura and malignant effusion, with cells that were positive for CK7 and thyroid transcription factor 1(TTF-1) and negative for CK20, p63, and calretinin. Testing for epidermal growth factor receptor (EGFR) mutation and ALK rearrangement was initiated, but the patient wanted to start treatment immediately rather than wait for test results, which typically requires 2 to 4 weeks. She was enrolled onto a clinical trial and was randomly assigned to receive standard pemetrexed-cisplatin. She experienced a partial response, but she had substantial symptoms, including nausea refractory to antiemetics and significant fatigue. She requested a break from chemotherapy after six cycles and developed symptomatic progression in the lung and pleura within 10 weeks. Meanwhile, molecular testing showed neither EGFR mutation in exons 19 or 21 nor ALK rearrangement in her tumor. The patient was reluctant to start second-line chemotherapy because of concerns about toxicity. She received palliative radiotherapy to the lung and growing pleural mass with some pain relief, and the palliative care team was consulted for additional support in symptom control. At this juncture, the adverse effects from chemotherapy have resolved, and she has an Eastern Cooperative Oncology Group performance status of 1. Second-line docetaxel is recommended, but she inquires about nonchemotherapy options.