Breast cancer is a multifaceted and diverse illness that impacts millions of people globally. Identifying the underlying causes of BRCA and creating efficient treatment plans are urgent. Necroptosis is widely involved in cancer development. However, the specific roles of necroptosis in cancer immunotherapy of breast cancer have not been explored. In this study, we aim to establish the connection between necroptosis and immunotherapy in BRCA. TCGA, METABRIC, GSE103091, GSE159956, and GSE96058 were included for bioinformatics analysis. NMF and CoxBoost algorithms were used to develop the necroptosis-related patterns and model, respectively. A necroptosis-related model was developed and determined KLRB1 as a critical tumor suppressor by in vitro validation. The mutation characteristics, immune characteristics, and molecular functions of KLRB1 were explored. We further examined how necroptosis-related KLRB1 functions in BRCA as a powerful tumor suppressor and regulates the activity of macrophages by in vitro validation, including CCK8, EdU, and Transwell assays. KLRB1 was also revealed to be an immunotherapy determinant.© 2024 The Authors.