The 2020 WHO Classification

<jats:p>The fifth edition of the World Health Organization Classification of Tumors of Soft Tissue and Bone was published in early 2020. The revisions reflect a consensus among an international expert editorial board composed of soft tissue and bone pathologists, geneticists, a medical oncologist, surgeon, and radiologist. The changes in the soft tissue tumor chapter notably include diverse, recently described tumor types (eg, atypical spindle cell/pleomorphic lipomatous tumor, angiofibroma of soft tissue, and <jats:italic toggle="yes">CIC</jats:italic>-rearranged sarcoma), new clinically significant prognostic information for a variety of existing entities (eg, dedifferentiated liposarcoma and solitary fibrous tumor), and a plethora of novel genetic alterations, some of practical diagnostic relevance (eg, <jats:italic toggle="yes">NAB2-STAT6</jats:italic> in solitary fibrous tumor, <jats:italic toggle="yes">FOSB</jats:italic> rearrangements in epithelioid hemangioma and pseudomyogenic hemangioendothelioma, and <jats:italic toggle="yes">SUZ12</jats:italic> or <jats:italic toggle="yes">EED</jats:italic> mutations in malignant peripheral nerve sheath tumor, leading to loss of H3K27 trimethylation). In this review, we highlight the major changes to the soft tissue chapter in the 2020 World Health Organization Classification, as well as the new chapter on undifferentiated small round cell sarcomas, with a focus on updates in diagnostic categories, prognostication, and novel markers. Recent discoveries in molecular genetics are also discussed, particularly those of immediate utility in differential diagnosis, including protein correlates detectable using immunohistochemistry.</jats:p>