The most common autoimmune disease associated with thymoma is myasthenia gravis. In addition, cellular and humoral immune defects have been frequently reported in association with thymic neoplasms. Here we report the case of a patient with myasthenia gravis receiving long-term immunosuppression with azathioprine and recurrent well-differentiated thymic carcinoma who developed CD4+ T-cell depletion and CNS cryptococcosis after multiple courses of chemotherapy and mediastinal irradiation. We hypothesize that in thymectomized patients bone marrow suppression and abrogation of the peripheral T-cell pool can result in a delayed T-cell regeneration due to the lack of functional thymic epithelium.