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Most resections for osteosarcoma received in surgical pathology laboratories these days are post-chemotherapy specimens. The tumor response to chemotherapy is an important prognostic indicator and pathologists are expected to provide an assessment of this feature when handling specimens. A typical post-chemotherapy specimen shows marked sclerosis with cell dropout as shown here. In between the densely sclerotic bony trabeculae, there are no viable tumor cells. Some cases show foci of coagulative necrosis or complete replacement of tumor by granulation tissue. Areas of cartilage in chondroblastic osteosarcoma are generally more resistant to chemotherapy.