Objective Tangential field irradiation in breast cancer potentially treats residual tumor cells in the axilla after sentinel lymph node biopsy (SLNB). In recent years, hypofractionated radiotherapy has gained importance and currently represents the recommended standard in adjuvant breast cancer treatment for many patients. So far, the impact of hypofractionation on the effect of incidental lymph node irradiation has not be addressed. Materials and methods Biological effective dose (BED) and tumor control probability (TCP) were estimated for four different hypofractionated radiation schemes (42.50 & x202f;Gy in 16 fractions [Fx]; 40.05 & x202f;Gy in 15 Fx; 27 & x202f;Gy in 5 Fx; and 26 in 5 Fx) and compared to conventional fractionation (50 & x202f;Gy in 25 Fx). For calculation of BED and TCP, a previously published radiobiological model with an alpha/beta ratio of 4 & x202f;Gy was used. The theoretical BED and TCP for incidental irradiation between 0 and 100% of the prescribed dose were evaluated. Subsequently, we assessed BED and TCP in 431 axillary lymph node metastases. Results The extent of incidental lymph node irradiation and the fractionation scheme have a direct impact on BED and TCP. The estimated mean TCP in the axillary nodes ranged from 1.5 & x202f;+/- 6.4% to 57.5 & x202f;+/- 22.9%, depending on the patient's anatomy and the fractionation scheme. Hypofractionation led to a significant reduction of mean TCP of lymph node metastases for all schedules. Conclusion Our data indicate that hypofractionation might affect the effectiveness of incidental radiotherapy in the axilla. This is particularly relevant for patients with positive sentinel lymph nodes who receive SLNB only.