Background: Necrotizing fasciitis (NF) is a rare, rapidly progressing, and potentially fatal tissue infection involving subcutaneous tissue, superficial fascia, and the overlying skin. Breast NF is often misdiagnosed because of the thick breast tissue between the skin and deep fascia. Only early diagnosis followed by prompt antibiotic treatment and surgical therapy can prevent disastrous consequences. There are many case reports on breast NF, but a systematic review is lacking. Methods: Using PubMed and Scopus we performed a systematic review of the literature covering a period of 20 years. We reviewed articles with predisposing comorbidities (risk factors), triggering factors, laboratory examinations, culture of organisms, antibiotic treatment, surgical interventions, the presence of septic shock, and final outcome. We also performed statistical tests of all these factors in relation to death. Results: Forty cases identified from 38 articles were included in our literature review. Twenty-one cases (52.5%) were primary, whereas 15 cases (37.5%) occurred after surgery. In 15 cases (37.5%), the single organism responsible for NF was Streptococcus pyogenes, whereas mixed organisms were found in 17 cases (42.5%). Surgical debridement was performed in 39 (97.5%) cases. Septic shock was found in all five (12.5%) deceased cases and was associated with patient's mortality (p < 0.001). Conclusions: Breast NF is a rare, severe, and easily misdiagnosed complication. Breast NF could differ from that in other body regions in etiology pattern and clinical manifestations. Confirmed diagnosis of breast NF is based on the combination of clinical, cultural, laboratory, and imaging findings. Urgent subsequent treatments, including surgical debridement, antibiotic therapy, and reconstructive surgery, are critical for better prognosis and survival of patients.