BACKGROUND Previous series concerning tamoxifen (TAM) rechallenge did not obtain satisfactory results. Using stricter criteria, we now assess the usefulness of readministration of TAM as an initial therapy for patients with recurrent breast cancer. METHODS The eligibility criteria were postmenopausal, estrogen receptor (ER) positive or unknown, at least 12 months of adjuvant TAM, a 6-month or longer drug-free period and no previous therapy after recurrence. A total of 10 patients were enrolled. TAM was administered in daily doses of 20 or 30 mg. RESULTS The mean age of the patients at the time of recurrence was 64.8 years. The receptor status was positive in 8 patients and unknown in 2. The median disease-free interval (DFI) after mastectomy was 71.7 months. A complete response was observed in one patient, a partial response in 6, stable disease in 2, and progression in one. The response rate was thus 70%, with an additional two patients showing no progression over 6 months. Although only one patient with a DFI of less than 48 months showed a positive response, all patients with a DFI longer than 48 months showed a clinical response. The duration of response was less than 12 months in 3 patients and longer in 4. CONCLUSIONS The post-adjuvant readministration of tamoxifen is a useful first choice therapy for postmenopausal recurrent breast cancer patients with positive ER and longer DFI.