Cutaneous hyperpigmentation, including melasma, solar lentigines, and post-inflammatory hyperpigmentation (PIH), results in a significant impact on patients’ quality of life. Unfortunately, many currently available over-the-counter (OTC) options have been limited by efficacy, safety, and tolerability concerns. Additionally, limited patient awareness and education on disease manifestation and root causes of hyperpigmentation often leave patients undiagnosed and untreated. Melanogenesis is driven by a complex pathway resulting in the ultimate production and deposition of melanin in the skin. The major rate-limiting step of melanogenesis centers on the conversion of L-Dopa to the final melanin product mediated by a cellular tyrosinase, causing the overproduction of melanin clinically resulting in hyperpigmentation. Recently, isobutylamido thiazolyl resorcinol (Thiamidol) has been identified as the most effective inhibitor of human tyrosinase out of 50,000 compounds screened, and thus, a novel ingredient for inclusion in OTC products to address hyperpigmentation. We describe here the current pre-clinical and clinical safety and efficacy data of Thiamidol formulations aimed at educating the dermatology community on a safe and effective OTC option for use as part of the overall management of hyperpigmentation in patients. Citation: Frey C, Grimes P, Callender VD, et al. Thiamidol: a breakthrough innovation in the treatment of hyperpigmentation. J Drugs Dermatol. 2025;24(6):608-616. doi:10.36849/JDD.9093.