Malignant Mesothelioma, or mesothelioma, is a mesothelial-based malignancy that may occur in the pleura, pericardium and peritoneum. Mesothelioma is a very aggressive cancer with limited treatment, and a median survival of about 1 year. At times, the diagnosis of mesothelioma may be problematic. The final diagnosis of mesothelioma relies on histology and often is dependent upon immunohistochemistry. It is generally assumed that mesotheliomas must stain positive for cytokeratin and calretinin and negative staining for these markers would rule out the diagnosis. We encountered a patient with a pleural-based, cytokeratin- and calretinin-negative sarcomatoid malignancy. These negative stainings would rule out the diagnosis of mesothelioma but, after careful consideration of the patient's clinical records, and additional histological and immunohistochemical studies, we conclude that this patient suffered from mesothelioma of the sarcomatoid type.