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Introduction: Talc pleurodesis is a well-established procedure performed to obliterate the pleural space to prevent recurrent pleural effusion and/or recurrent pneumothorax. Pleurodesis is commonly accomplished by draining the pleural fluid, if present, followed by either a mechanical procedure, such as abrasion, pleurectomy, or instillation of a chemical irritant into the pleural space, which results in inflammation and fibrosis which obliterates the pleural space. The reported complications of talc pleurodesis are hypoxemia, hypotension, tachycardia, dyspnea, chest pain, and fever., Case Presentation: Herein, we present a case of a 43-year-old female patient who developed an intense mesothelioid reaction which occurred 7 years following talc pleurodesis., Conclusion: This case represents a unique mesothelioid reaction which became manifested several years after recurrent talc pleurodesis. Such a mesothelioid reaction can clinically and radiographically mimic malignant mesothelioma. We conclude that Talc pleurodesis played a causative role in this patient developing an intense mesothelioid reaction. A mesothelioid reaction should be included in the differential diagnosis in patients with pleural thickening/pleural plaque formation who have previously been treated with talc pleurodesis.