Osteopoikilosis is a rare benign osteosclerotic bone disorder that may be misdiagnosed as skeletal metastases. Here we describe a case of coincidental breast cancer and osteopoikilosis mimicking skeletal metastases. A 41-year-old woman underwent right modified radical mastectomy in April 2007. Twenty-eight months after initial treatment, the patient complained of bilateral knee and foot pain. Plain X-rays of the feet and knees showed multiple well-defined osteosclerotic lesions. According to the radiographic appearance, the most likely differential diagnoses included skeletal metastases from breast cancer and osteopoikilosis. A whole-body bone scintigraphy showed no increase in uptake by the sclerotic lesions, and serum lactic dehydrogenase, carcinoembryon- ic antigen, alkaline phosphatase and cancer antigen 15-3 were not elevated. We therefore diagnosed the patient’s skeletal lesions as osteopoikilosis. This case and our literature review suggest that the radiographic appearance of osteopoikilosis may mimic or mask skeletal metastases, potentially leading to misdiagnosis in patients with cancer.