The diagnosis of osteosarcoma can be challenging, given the diverse histologic patterns, limited biopsy samples, lack of tumor-specific molecular alterations, and necessity for radiologic correlation. This review summarizes the key pathologic features of osteosarcoma subtypes with an emphasis on illustrating radiologic, gross macroscopic, and histologic features to help pathologists with classification. In addition, the authors provide an update on recent advances in molecular genetics and summarize pertinent differential diagnoses.