The effects of tamoxifen (TAM), medroxyprogesterone acetate (MPA), their simultaneous combination or an alternating sequential combination of TAM plus MPA (TAM-MPA), was evaluated in 52 patients with advanced or recurrent breast cancer in a randomized controlled trial. The response rates of TAM, MPA, TAM & MPA, and TAM-MPA were 13.3%, 36.4%, 7.1% and 25.0%, respectively. All four therapies showed a higher response rate in the patients with soft tissues or with no previous therapy. However, there were no significant differences between the patient's characteristics and response rate among these four therapies. The differences in the frequency of adverse effects among these therapies were not significant, and there were no severe adverse effects with any therapy. In the cross-over trial of TAM and MPA, although 15.4% of patients who failed to show a response to TAM showed an objective response to MPA, no response to TAM was seen in the patients who had failed to show a response to MPA. In conclusion, TAM & MPA was not more effective than TAM or MPA, and TAM-MPA was not more effective than MPA. Adverse effects were not increased with TAM & MPA or TAM-MPA. MPA was useful as a second-line therapy after TAM.