Introduction: Malignant mesothelioma(MM) is an aggressive tumor of serosal surfaces. There is a dilemma for diagnosis of MM because of the many morphologic similarities between neoplastic cells and their benign counterparts. We assumed that there is a change in p53 expression with transformation from reactive hyperplasia to MM. Case Report: In 2004, a 65 year old male presented with left pleuritic chest pain. He had been worked as a supervisor of factory of asbestos-containing products in past 20 years. Chest computed tomography(CT) showed moderate amount of left pleural effusion with some loculation and also, combined mild pleural thickening and subtle enhancing area. Pathologic diagnosis was reactive mesothelial hyperplasia. In 2008, he felt left pleuritic chest pain. Chest CT showed progressive thickening of the left pleura with nodularity. Pathologic diagnosis was atypical mesothelial hyperplasia. In 2011, chest CT showed progressive thickening of the left pleura. Pathologic diagnosis was well differentiated papillary mesothelioma. We analyzed the serial change as immunohistochemistry staining for p53 of pleural tissues obtained by VATS in this patient. The result revealed negative p53 stain with diagnosis of reactive mesothelial hyperplasia in 2004 and 2011. Positive conversion of p53 staining was showed with atypical mesothelial hyperplasia in 2008. Conclusion: P53 expression can changes during transformation from reactive hyperplasia to atypical hyperplasia and malignant mesothelioma. P53 staining may be helpful for early diagnosis of malignant mesothelioma.