CASE PRESENTATION: A 48-year-old male smoker (30 pack years), with negative family history for malignancies, was admitted in the Pneumonology dept of Corfu’s General Hospital with right chest pain. Four years before, the patient had undergone talc pleurodesis for right-sided relapsing primary spontaneous pneumothorax. Physical ad biochemical examinations, malignancy markers included, were negative. Chest Radiograph and CT revealed a peripheral longitudinal consolidation in the right upper lung field, along the pleural surface, and an osteolytic lesion of the right 3rd rib. Bronchoscopy was negative for endobronchial lesions. Biopsy of the lesion described multifocal presence of moderate to low-differentiated adenocarcinoma in the lung segments and in the visceral pleura. The neoplasmatic cells were strongly positive for cytokeratin 7 and p63, weakly positive for cytokeratin 18 and focally positive for cytokeratin 19. The markers for TTF-1, napsin, CD31, CD34, WT-1, calretinin, cytokeratin 20 and cytokeratin 14 were negative. Further patient investigation for other primary or metastatic lesions was negative. The patient followed a chemotherapy schedule with Carboplastin, Pemetrexed and Bevacizumab without any response. Local Radiotherapy and second line chemotherapy with Docetaxel were also unsuccessful and the patient died 11 months after the diagnosis.