The combined administration of antiangiogenic agents (AA) and radiation is being evaluated. No AA has yet received Marketing Authorization in this indication. However, they are widely used in medical oncology and criteria for stopping their administration in case of irradiation have not been defined. We report the case of a 63-year-old man experiencing grade 2 skin toxicity while on radiation treatment and sorafenib (400mg twice daily) for a metastatic lesion developing between the vastus medialis muscle and the cortical of the mid-diaphysis of the right femur. Toxicity occurred at 21Gy, for a total dose of 36Gy (12 fractions of 3Gy). Cutaneous symptoms rapidly disappeared after treatment discontinuation. Radiotherapy alone was resumed after a few days and the total dose could be delivered, with good tolerance. At 2-month follow-up, the intramuscular lesion had regressed. Several other cases of patients with poor tolerance to the association of AA and radiotherapy have been reported. Further studies of the effectiveness and tolerance of the combination treatment are needed before indications for AA can be extended to other diseases.