Diagnosis of osteosarcoma can be challenging because of its diverse histological patterns and the lack of diagnostic biomarkers for most examples. This review summarizes the key pathologic findings of osteosarcoma subtypes (high-grade central, parosteal, low-grade central, periosteal, high-grade surface, and secondary) with an emphasis on describing and illustrating histological heterogeneity to help general pathologists. Differential diagnoses are listed for each entity, and histological subtype and distinguishing features, including molecular genetic findings (eg, MDM2, IDH, H3F3A, FOS, and USP6), are discussed. The review also covers recently established and emerging concepts and controversies regarding osteosarcoma.