To determine the risk factors associated with the recurrence and metastasis of breast cancer after lumpectomy with postoperative radiation therapy, 112 cases were studied who had been treated during a period of 11 years at the University of Florida Health Science Center/Jacksonville. The patients were evaluated for their age, race, and clinical stage, as well as the tumor grade, stage, histological type, and node involvement. Among these cases, four (4%) recurred locally within a year of treatment; 10 (9%) cases presented with distant metastasis within three years. No obvious clinical risk factors were identified for local recurrence; however, positive-node status seemed to be associated with distant metastasis. The primary tumors of these cases were then studied using immunohistochemical staining to evaluate the potential prognostic value of tumor markers such as estrogen receptor (ER), progesterone receptor (PR), tumor suppressor gene p53, HER-2/neu oncogene, and multi-drug resistance gene (MDR). The expression of p53 was associated with all local recurrence cases as well as 50% of those who had metastasis. The expression of MDR was observed in 80% of the distant metastatic cases. This preliminary result may warrant further studies on larger number of cases to assess the predictive value of p53 and MDR in the outcome of breast cancers in patients treated with postoperative radiation therapy.