Cryptococcal infection results from inhalation of fungal spores and usually is confined to the lungs, but may disseminate systemically. Radiologically, cryptococcal infection has multiple forms of presentation. The diagnosis is usually based on fungal isolation from cultured clinical specimens. Long term antifungal therapy is recommended, but surgical procedures may eventually be necessary when large thoracic symptomatic masses are present. We report a case of a 41-year-old male, immunocompetent, investigating a palpable mass in the left supraclavicular region associated with unintentional weight loss over the last three months. He also reported chest pain in this period. Chest X-ray, ultrasonography, and computed tomography were performed, which diagnosed a mediastinal and left supraclavicular mass, interpreted as lymph node conglomerates of unknown etiology. He also underwent a biopsy of the left supraclavicular mass for etiological determination by histopathology, which confirmed cryptococcosis infection. Although very infrequent, mediastinal cryptococcal infection (simulating masses) is a challenging but important differential diagnosis of benign and malignant lesions, since its treatment is usually clinical.