This group is sister to all other loricariids except Lithogenes.

Monophyly for the family is strongly supported, except, possibly, the inclusion of Lithogenes.

As members of Loricariidae, Lithogenes species have a suckermouth.

However, unlike most loricariids, Lithogenes possesses armor plating only on the latter half of the body.

An undescribed species of Lithogenes is known from the Orinoco basin of the Guiana Shield.

It is the only genus within the subfamily Lithogeneinae.

Neoplecostominae are the most basal group among the loricariids with the exception of Lithogeneinae.

Relative to an undescribed species of Lithogeneinae, L. valencia has sister group relationship to L. villosus.

Under Ambruster, six subfamilies are recognized: Delturinae, Hypoptopomatinae, Hypostominae, Lithogeneinae, Loricariinae, and Neoplecostominae.