As a well-known trademark, legal protection to guarantee the mark is definitely required to prevent mark violation. A well-known trademark is a trademark which holds a high reputation and substantive similarity is a resemblance caused by the presence of elements which stands out between one trademark and other. Pursuant to the abovementioned explanation, such matter occurred in the case of trademark between “Neurobion” and “Bioneuron” regarding trademark cancellation within verdict number 52/Pdt-Sus-Merek/2014/Pn.Jkt.Pst. Whereas, within the said verdict it is proven that the mark owned by the Defendant contains substantive similarity with the well-known trademark owned by the Plaintiff. Verdict number 52/Pdt-Sus-Merek/2014/Pn.Jkt.Pst was then strengthened by Cassation Verdict number 49K/Pdt-Sus-Merek/2015. Based on the said issue, the analysis which will be conducted uses the juridical normative research by using secondary data and case approach; normative approach; and conceptual approach. Therefore, the existence of regulations concerning well-known trademark is highly required and such can be seen by the transition of Trademark Law from Law Number 15 Year 2001 regarding Trademarks to Law Number 20 Year 2016 regarding Trademarks and Geographical Indications which gives rise to similarity and differences between both Laws in explaining regarding well-known trademark and substantive similarity. Further, pursuant to the Commercial Court verdict, the basis of the judge’s consideration in deciding a mark which contains a substantive similarity and whether such matter has been in line with the prevailing well-known trademark regulations can be seen.