Purpose Red breast syndrome (RBS) was first described in association with dual-plane direct-to-implant reconstruction utilising silicone implants and biological matrixes or synthetic meshes. It is an uncommon, but known sterile inflammatory condition occurring during the post-operative period characterised by local erythematous skin change and has previously been thought to be caused by the use of acellular dermal matrix or synthetic mesh. We describe a case of red breast syndrome in a prepectoral reconstruction where no mesh was used, and summarise our experience with this condition so far. Methodology This is a case study of a premenopausal 50-year-old female with right breast cancer detected on screening. She had no positive family history and no regular meds or allergies. She underwent a right nipple-sparing mastectomy, sentinel node biopsy and pre-pectoral implant reconstruction without mesh using Mentor CPG implants. Results The patient was diagnosed with RBS at 25 days post-operatively after presenting with itch and erythema. She was treated with antibiotics, topical steroids and antihistamines for 5 days. Her condition worsened and was subsequently escalated to oral prednisone, which resulted in complete resolution of her symptoms. She did not experience any wound issues or seroma formation. Conclusion RBS can occur without mesh in post-mastectomy implant-based breast reconstruction, indicating a potential paradigm shift.