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Malignant pleural mesothelioma is usually a fatal disease and is considered a locally aggressive tumor. Consequently, distant metastases are very rare and a diffuse involvement of the lung is seldom reported. However, due to more efficient chemotherapy protocols and aggressive management strategies including induction chemotherapy followed by extrapleural pneumonectomy and adjuvant high-dose hemithoracic radiation therapy, so called trimodality therapy, survival is prolonged in selected patients. Therefore, new presentations of the disease are appearing with new diagnostic and therapeutic challenges. Herein, we report two cases of treated mesothelioma patients who developed a miliary mesothelioma in the remaining lung 36 and 41 months after undergoing multimodal therapy. Diagnostic assessment and therapeutic strategy are discussed taking into account the different evolutions of each patient.