Malignant pleural mesothelioma (MPM) is a highly aggressive cancer of the pleura with a well-established male predominance and causative link with asbestos exposure. We report four cases of female patients with MPM referred for palliation of symptoms thought to be due to previous non-pleural malignancy.With emerging novel treatments for MPM, this article discusses four unusual cases of MPM occurring in the setting of other malignancy, highlights the importance of considering a primary diagnosis of MPM even in patients with other malignancy, and reinforces the benefits of video-assisted surgical biopsy which allows simultaneous diagnosis and treatment.