Distinguished from all congeners, except those belonging to the Hypostomus cochliodon group, by having few teeth (10 to 13) bearing a small lateral cusp and acutely angled dentaries. Diagnosed from the remaining members of the Hypostomus cochliodon group, except H. hemicochliodon, H. sculpodon, H. soniae Hollanda, Carvalho & Weber, and H. weberi, by possessing bicuspid teeth with mesial cusp rounded, considerably larger than outer cusp (vs. teeth generally unicuspid, outer cusp, if present, almost imperceptible, mesial cusp large and distinctly spoon-shaped). Hypostomus kopeyaka can be distinguished from H. hemicochliodon, H. sculpodon, H. soniae, and H. weberi by a distinctive color pattern composed of conspicuously horizontally elongated, closely-set black spots on the head and dorsal surfaces of the body (vs. spots absent in H. soniae, spots present but rounded in the remaining species, spots small in H. hemicochliodon and H. sculpodon, and large and widely-set in H. weberi). Additionally, it is differs from all the members of the Hypostomus cochliodon group, except H. weberi, H. ericae Hollanda Carvalho & Weber, H. hemicochliodon, H. paucipunctatus Hollanda Carvalho & Weber, H. sculpodon and H. waiampi Hollanda Carvalho & Weber, by possessing a buccal papilla (Ref. 83896).