Accelerated partial breast irradiation Florence phase 3 trial is a single-center study comparing intensity-modulated based accelerated partial breast irradiation (PBI, 30 Gy in 5 fractions) and whole breast irradiation (50 Gy in 25 fractions) followed by a tumor bed boost (10 Gy in 5 fractions). This easy-to-deliver PBI approach showed excellent long-term disease control with favorable safety and cosmetic outcome profiles. A plateau has been probably reached concerning the reduction of the number of fractions in the postoperative PBI setting. A 5-fraction schedule is the standard regimen and probably the appropriate compromise in terms of efficacy, safety, and quality of life, also considering the negative results of most intraoperative single-fraction PBI trials. A new frontier is now open on the potential benefit of preoperative PBI delivery, although concerns remain on the optimal dose, fractionation, and technique. Hereby we report the accelerated PBI Florence phase 3 trial experience and future perspectives.