Musculoskeletal pain is a common presenting complaint among pediatric and adult patients. The differential diagnosis for a patient with musculoskeletal pain is vast and encompasses a plethora of pathophysiology. In this chapter we examine the case of an adolescent patient who is presenting with chronic, atraumatic thigh pain. While exceedingly rare, musculoskeletal neoplasia is one cause of musculoskeletal pain that you do not want to miss. The list of benign and malignant bone and soft tissue tumors that may occur in an adolescent patient is extensive. Osteosarcoma most commonly arises in patients during their second decade of life and is the most common primary malignant bone tumor in children and adolescents. This case presentation and chapter discussion on osteosarcoma are designed to help students and physicians better recognize, understand, and manage patients with this neoplasm.