Hypostomus pantherinus was described by Kner in 1854 based on a single young specimen collected by Natterer with a type-locality just asserted as Guaporé. No robust scientific paper focusing the distribution, taxonomy and ecology of this species has been published since the description. Here, based on the analysis of the holotype, recently collected material, and on an extensive searching on ichthyological fish collections, H. pantherinus Kner 1854 is redescribed and its geographical distribution is established to be in the rio Iténez-Guaporé and the mouth of its Bolivian and Brazilian tributaries. Hypostomus pantherinus is distinguished from congeners mainly by villiform teeth, conspicuous black, sharp and widely spaced spots on head, and dark blotches on trunk and fins, keels along lateral series of plates, sharp crests on supraoccipital and on compound pterotic-supracleithrum, less than 25 spots on compound pterotic-supracleithrum, one blotch per interradial membrane along each row on dorsal fin, and by usually attaining about 160 mm SL in size.