The general features of several important mineral deposits of polymetallic character in the Republic of Northern Macedonia that have been actively exploited in the past are described. These include the Buchim copper mine and Sasa, Zletovo and Toranica lead-zinc mines, as well as some ore prospects that have been extensively explored for years. In addition, sites with known ore reserves, but which are not yet at the exploitation stage are presented, including Plavica, Ilovica, Kadiica, Borov Dol and others. The elaborated RIS-RESERVES program is used to affirm numerous parameters related to the definition of ore reserves in the deposits, and has now provided the opportunity for preparation of an overview which shows the major metallogenetic characteristics of the deposits with their techno-economic parameters. This approach enables affirmation of the potential of the polymetallic ore deposits in the Republic of Northern Macedonia.