Objective: We report two cases of atypical femoral fracture (AFF) in patients with cancer. Patients: Two patients, a 53-year-old woman with breast cancer and a 77-year-old man with prostate cancer, could not walk after being injured in a fall. They used bone-modifying agents (BMA) for the prevention of bone metastasis for three and four years, respectively. Results: Intramedullary nails were placed to fix the femoral fractures in each patient. Neither of them had pathological metastatic femoral fractures based on fracture site specimens; however, severe suppression of bone turnover at the fracture site was suspected. Both patients could ambulate with a T-cane and were free of hip pain after surgery. Radiographs showed no callus formation at the fracture site. Conclusion: Based on the two cases of AFF in patients with cancer related to BMA use, we should consider that the incidence of AFF may be associated with long-term BMA use.