The differential diagnosis of mediastinal masses involves many benign and malignant conditions, such as lymphadenopathies and cystic lesions. Metastatic mediastinal adenopathies are usually due to lung, esophagus, and stomach cancer and, rarely, due to colorectal cancer. Gastrointestinal duplication cysts are uncommon inherited lesions usually diagnosed during childhood and may involve the esophagus in 20% of cases. In adults, they are usually asymptomatic and diagnosed incidentally. We report the case of a 54-year-old male who recently underwent sigmoidectomy due to an obstructive colon adenocarcinoma. Staging computed tomography scan showed a hypodense lesion in the posterior mediastinum suggestive of metastatic adenopathy. Endoscopic ultrasound revealed a homogeneous and hypoechogenic lesion with intramural location in the upper esophagus, suggestive of a duplication esophageal cyst. Given the oncologic background and to exclude metastatic disease, endoscopic ultrasound-guided fine needle aspiration was performed, and a mucinous fluid was aspirated. The cytologic examination supported the ultrasonographic diagnostic hypothesis. This case highlights the role of endoscopic ultrasound in the differential diagnosis of mediastinal masses, particularly in oncologic patients, in order to rule out more ominous lesions.info:eu-repo/semantics/publishedVersio