Rationale: Eosinophilic pleural effusion (EPE) is a rare phenomenon in which the etiological diagnosis remains a challenging issue; here, we present a patient who was eventually diagnosed with malignant EPE by parietal pleural biopsy. Patient concerns: The patient was a 73-year-old man with pulmonary tuberculosis who was taking isoniazid and rifampin; after 6 months, he had right-sided eosinophilic pleura, and histopathological examination of the parietal pleura revealed malignant cells from the lung. Diagnosis: Based on the parietal pleural biopsy, the patient was diagnosed with lung adenocarcinoma with ipsilateral pleural metastasis stage IVA. Interventions: The patient received a first-line systemic chemotherapy regimen (premetrexed and carboplatin). Outcomes: The patient received 2 cycles of chemotherapy, and based on the response evaluation criteria for solid tumors, he achieved partial response and the effusion disappeared. Lessons: This case presents a patient with tuberculosis who was suffering from an EPE, which was eventually diagnosed as malignant EPE based on histopathological examination through medical thoracoscopy, although multiple Thinprep cytology tests showed no evidence of malignancy, pleural biopsy is necessary to obtain an accurate etiology diagnosis.