Background: Invasive thymoma is a rare mediastinal tumor. Clinicopathological characteristics that influence survival of patients with this tumor are under debate. Treatment is based on tumor resection. The benefice of therapies, such as radiation therapy (RT) and/or chemotherapy (CT) as adjuvant treatments to surgery, or palliative therapy to unresectable or recurrent thymoma are discussed. Objectives: The aim of this study was to assess patients with invasive thymoma, with specific emphasis on factors predicting survival. Methods: We studied retrospectively 23 patients with invasive thymoma. Parameters assessed were age, presenting symptoms, histological features, stage at diagnosis, treatment modalities and survival. All patients received primary therapy: 11 patients (48%) had tumor resection associated with CT and/or RT, while 12 patients had palliative therapy including RT and/or CT. Regimens for CT were based on cisplatin. Results: Patients’ mean age was 58 years. Three patients had stage II disease at diagnosis (13%), 8 patients had stage III (35%) and 12 patients had stage IV (52%). Median overall survival was 20 months (range: 4–160) and five-year survival rate was 43.5% (10 patients). Surgical resection had a significant impact on survival (p < 0.0001). Survival was also related to stage of the disease at diagnosis (p = 0.006), but not to histology of the tumor (p = 0.12). Salvage treatment was of clinical importance: 5 out of 15 patients (33.3%) who relapsed during a 5-year follow-up responded to a multimodality therapeutic approach that affected survival (p = 0.019). Conclusion: Factors determining the outcome of these tumors are the stage of the disease at diagnosis, and the adequacy of surgical removal. Salvage treatment of recurrent thymoma may give a moderate response rate and improve survival.