Surgery remains the mainstay of treatment for breast cancer, including complete or partial mastectomy and lumpectomy. Breast reconstruction has gained popularity mainly due to its tremendous impact on the psychological status of the patients. Autologous fat grafting is a well-established method used in cosmetic surgery; however, fat re-absoprtion, fat necrosis, calcifications and oil-cyst formation are some usually encountered complications limiting the efficacy of this approach. Platelet-rich plasma (PRP) has recently been postulated as a promising method for tissue regeneration since it contains high levels of diverse human growth factors. To date, preliminary results from clinical studies regarding the combination of PRP and fat grafting in breast reconstruction have shown ambiguous results, whereas preclinical studies are more favorable. However, concerns have been raised regarding the extent of cellular promotion induced by PRP application and the corresponding potential malignant transformation. The aim of our study was to present, analyze and critically evaluate the role of PRP in breast reconstruction after breast cancer surgery in terms of efficacy and oncological safety highlighting the caution that needs to be taken in order to eliminate any chance of recurrence in patients who have theoretically undergone complete excision of the tumor burden.