Aims and background The aim of this retrospective multicenter study was to evaluate the impact of progesterone receptor (PgR) loss on locoregional recurrence in patients with estrogen receptor (ER)-positive primary breast cancer and ER-positive locoregional recurrence. Patients and Methods Eight Italian oncology centers collected data from consecutive patients with ER-positive breast cancer and a subsequent ER-positive locoregional recurrence. Results Data were available for 265 patients diagnosed with breast cancer between 1990 and 2009. Median metastasis-free survival was 111 months in patients with PgR-positive primary tumors and locoregional recurrence (PgR^pos), 38 months in patients with PgR-negative primary tumors and locoregional recurrence (PgR^neg), and 63 months in patients with PgR-positive primary tumors and PgR-negative locoregional recurrence (PgR^loss). In multivariate analysis, PgR status was independently associated with metastasis-free survival, with a hazard ratio of 2.84 (95% CI 1.34-6.00) for PgR^neg compared with PgR^pos, and 2.93 (95% CI: 1.51-5.70) for PgR^loss compared with PgR^pos. Conclusions PgR absence was found to be a negative prognostic factor in breast cancer patients with ER-positive locoregional recurrence. Thus, PgR status could be a biological marker in ER-positive recurrent breast cancer.