The clinical scenario of a pulmonary nodule following lung transplantation is one with limited experience and no supporting guidelines for the approach to diagnosis and management. Given the broad differential diagnosis for pulmonary nodules in this setting, most of which are life-threatening without appropriate treatment, aggressive evaluation is required. Here we present a case of a 70-year-old female with the development of a large pulmonary nodule in the native lung four years following a single lung transplant. She underwent bronchoscopy with endobronchial ultrasound to achieve a tissue diagnosis which showed small cell lung carcinoma. The patient was started on chemotherapy and has shown clinical and radiographic improvement at most recent follow up seven months after the initial diagnosis. In this report we discuss the differential diagnosis and corresponding imaging findings for the pulmonary nodule following lung transplantation to aid in guiding clinicians navigate this challenging clinical situation.Copyright © 2020 Elsevier Inc. All rights reserved.