Tazemetostat (Tazverik™), a first-in-class, small molecule enhancer of zeste homolog 2 (EZH2) inhibitor, received accelerated approval in January 2020 in the USA for the treatment of adults and adolescents aged ≥ 16 years with locally advanced or metastatic epithelioid sarcoma not eligible for complete resection. Developed by Epizyme, in collaboration with Eisai, it is the first therapy to be approved specifically for the treatment of epithelioid sarcoma in the USA. The recommended dosage regimen is 800 mg twice daily, administered orally with or without food, until disease progression or unacceptable toxicity. Tazemetostat is also undergoing clinical development in various countries worldwide for use in several other tumour types, including diffuse large B-cell lymphoma and mesothelioma, with the US FDA accepting a New Drug Application and granting priority review for its use in the treatment of follicular lymphoma. This article summarizes the milestones in the development of tazemetostat leading to this first approval for the treatment of adults and adolescents aged ≥ 16 years with locally advanced or metastatic epithelioid sarcoma not eligible for complete resection.