As mentioned previously, observation of cysts is often a better way to differentiate the amoeba. The most important characteristics to look for are: number and appearance of nuclei, presence and appearance of chromatoid bodies, and presence of glycogen. Chromatoid bodies are dark staining, rod-like structures in the cytoplasm.
As shown in Table 5, E. histolytica cysts are most similar to E. harmanni and E.coli cysts. The major point of differentiation is that E. histolytica cysts have 1-4 nuclei visible, but E. coli cysts generally have up to 8 or more. E. hartmanni have 1-4, but they are notably smaller.
Cysts are stained with trichrome unless otherwise noted.
Table 5. Differentiating Amoeba Cysts.| Organism | Image | Nuclear Characteristics | Cytoplasm |
| E. histolytica Spherical 10-20 μm;
(usually 12-15 μm) | 
Trichrome; arrow points to chromatoid body (12) Wet mount; arrow points to nuclei seen (13) | 1-4 nuclei Peripheral chromatin: fine, evenly distributed Karyosome: small, compact, usually central | May contain chromatoid bodies which are blunt or rounded with smooth edges |
| E. coli Spherical or oval 10-35 μm | (14)
Iodine stain - 6-7 nuclei visible | Mature cyst: 8 nuclei (occasionally as many as 16) Peripheral chromatin: course, granular Karyosome: large, eccentric or central | May contain chromatoid bodies which appear splinter shaped, with rough edges |
| E. hartmanni Spherical 5-10 μm; (usually 6-8 μm) | 
(15) | 1-4 nuclei (2 nuclei common) Peripheral chromatin: fine, evenly distributed granules Karyosome: small, compact, central | Usually contain chromatoid bodies which are elongated, blunt ends, smooth |
| E. nana Oval 5-10 μm; (usually 6-8 μm) | 
(16) | Usually 4 nuclei Peripheral chromatin: none Karysome: smaller than the troph, but larger than the Entamoeba spp. | Small granules or inclusions common Chromatoid bodies: rare but fine linear chromatoidals can occasionally be seen |
| I. butschlii Oval or round 5-20 μm;
(usually 10-12 μm) | 
(17) | Mature cyst: 1 nucleus No peripheral chromatin Karyosome: large, eccentric, refractile granules may be on one side | Occasional granules No chromatoid bodies Most notable: large, compact, well defined glycogen |
