Megestrol acetate as initial hormonal therapy produced a 40% objective response rate in 53 patients with advanced breast cancer; another 26% achieved stable disease. For 19 patients with visceral-dominant disease, the response rate was 42%. To investigate the effect of the order of sequential hormonal therapy, records of 66 patients treated with tamoxifen before megestrol acetate or with megestrol acetate before tamoxifen were reviewed retrospectively. Of the 24 patients who were given megestrol acetate first, nine (38%) had objective response to primary therapy, and four (17%) to secondary therapy. Among the 42 patients treated with tamoxifen first, there were nine (21%) objective responses to primary therapy and eight (19%) responses to secondary therapy. Results show that megestrol acetate is effective first-line hormonal therapy for advanced breast cancer. Megestrol acetate can be used as primary hormonal therapy and tamoxifen as secondary hormonal therapy, as an alternative to the more usual reverse order. One may also consider megestrol acetate for some advanced breast cancer patients with visceral-dominant disease.