The principal issue in the classification of parasome-containing amoebae is to determine which if any of the few available characters, which are not congruent, most accurately reflect the evolutionary history of these organisms.

It does appear that naked amoebae ("gymnamoebae") with lobose pseudopodia, tubular mitochondrial cristae, mesomitotic nuclear division, and no flagellate stages in the life history, form a "natural group" (a "clade"). Paramoeba may then be assigned with some confidence to the phylum Rhizopoda and class Lobosea. The challenges arise at the ranks of order and below.

The International Code of Zoological Nomenclature is the applicable code.

1. Issues at the ranks of family and genus

The family Paramoebidae was created by Poche (1913) to accommodate the parasome-containing amoebae (then P. eilhardi, P. pigmentifera, and P. chaetognathi). At that time, the presence of the parasome was the principal determinant. Poche, however, also gave credence to reports of flagellate reproductive stages in these species; these reports have since been refuted (Hollande 1940, 1980). Differences in locomotive form were not considered useful.

Later, the locomotive form took on greater importance. Chatton (1953) separated Janickina from Paramoeba on this basis, a decision supported by Page (1970) and Hollande (1980). Page (1970) discussed the possibility of merging Paramoeba into Mayorella, whose species closely resemble Paramoeba species in locomotive form but lack parasomes.

The electron microscope provided additional characters, most of them associated with the cell surface. Grell and Benwitz (1966) discovered scales on the surface of P. eilhardi. Cann and Page (1982) discovered a glycocalyx (surface coat) on P. pemaquidensis and P. aestuarina that was subdivided into hexagonal "glycostyles". Janickina has the glycocalyx but no glycostyles (Hollande 1980). Other species appear to have unornamented cell membranes (e.g. P. invadens; Jones 1985).

On the basis of locomotive cell morphology and limited sets of ultrastructural characters, Hollande (1980) removed Janickina from the Paramoebidae and referred it to Lobosea incertae sedis. Subsequently, Page (1987), using similar criteria, created the new genus Neoparamoeba for the two species with hexagonal glycostyles. He removed Neoparamoeba from Paramoebidae and added it to the family Vexilliferidae Page, 1987, together with two genera having similar morphology and ultrastructure but lacking parasomes, Pseudoparamoeba and Vexillifera.

At the same time, Page added two genera to the Paramoebidae, both of which lack parasomes: Mayorella and Korotnevella (given as "Dactylamoeba" in the Page paper).