Presence of any of the following concerning clinical or imaging findings would result in a Bone-RADS4 designation: history of malignancy with propensity for bone metastases, pain attributable to the lesion, cortical involvement, soft tissue extension, pathologic fracture, surrounding bone marrow edema, solid mass-like enhancement, a lesion in the sternum in a patient with breast cancer (Fig. 10), or elevated prostate-specific antigen (PSA) [52]. The gene discussed is KLK3; the disease is breast cancer.