We report the diagnostic challenges raised by the uncommon synchronous finding of a lung sequestration and foregut cyst in a 76-year-old male scheduled for radical treatment of his colonic cancer. Following a computed tomography (CT) scan of the chest and a combined positron emission tomography (PET)-CT scan these lesions initially suggested a primary lung cancer with single-station mediastinal nodal disease. At the end of an inconclusive non-invasive diagnostic pathway, histopathologic diagnosis was obtained by video-assisted thoracoscopy, converted into a limited thoracotomy. Even though advanced imaging techniques are providing an overall improvement in diagnostic accuracy, invasive biopsy continues to represent an additional option in complex cases.