Osteopoikilosis, a rare benign bone disease, is usually an incidental radiographic finding without therapeutic considerations. It is characterized by multiple sclerotic bone lesions, which are asymptomatic in most of cases. The challenge is to distinguish osteopoikilosis from other, especially malignant, bone diseases. In this case report, we present a 65-year-old male patient, who was incidentally diagnosed with osteopoikilosis in our department. The diagnosis was based on the exclusion of differential diagnosis, typical imaging findings in X-rays, CT scan and PET/CT scan. In this work, we discuss recent literature on the disease, including prevalence, pathogenesis, clinical manifestation, as well as differential diagnosis.