We report on a series of consecutive patients with localized radiation-associated angiosarcoma (RAAS) of the breast region (BR) treated at two Italian sarcoma reference centers. We retrospectively reviewed all cases of primary, localized, resectable RAAS of the BR, treated at one of the two participating institutions from 2000 to 2019. Relapse-free survival (RFS) and overall survival (OS) were calculated. The prognostic role of several variables was investigated. A propensity score matched (PSM) analysis was carried out. Eighty-four patients were retrospectively identified. Nineteen out of 84 patients (22.6%) were pretreated with an anthracycline-based regimen for previous cancer. All patients but one underwent surgery, with 37/84 (44.1%) receiving surgery alone and 46/84 (54.8%) a multimodal approach: 18/84 (21.4%) received radiation therapy (RT) and 46/84 (54.9%) received chemotherapy. An anthracycline-based regimen was used in 10/84 patients (11.9%), while a gemcitabine-based regimen was used in 33/84 (39.3%). With a median follow-up of 51 months (interquartile range: 30-126 months), 36/84 patients (42.9%) relapsed and 35/84 patients (41.7%) died (8/84, 9.5% in the lack of metastatic disease). Five-year OS and 5-year RFS were 57% 95% confidence interval (CI) 43% to 68% and 52% (95% CI 39% to 63%), respectively. Both (neo)adjuvant RT and chemotherapy were associated with better RFS hazard ratio (HR) 0.25, 95% CI 0.08-0.83; HR 0.45, 95% CI 0.23-0.89 with a trend towards a better OS (HR 0.51, 95% CI 0.18-1.46; HR 0.60, 95% CI 0.29-1.24). Gemcitabine-based regimens seemed to perform better (HR 4.28, 95% CI 1.29-14.14). PSM analysis retained the above results. This retrospective study supports the use of (neo)adjuvant RT and chemotherapy, in primary, localized resectable RAAS of the BR. An effort to prospectively validate the role of (neo)adjuvant RT and chemotherapy is warranted. •A multimodal approach improves outcomes of radiation-associated breast angiosarcoma.•The incorporation of a gemcitabine-based chemotherapy in the (neo)adjuvant setting should be encouraged.•An effort for a prospective validation of these results in specific angiosarcoma patient populations is warranted.