Like many cactuses its populations are sometimes threatened by this desirability due to the theft or removal of plants from the wild by collectors.

[3] The spines arrayed around the center (radial) number 12 to 35 per cluster, are 3–13 millimeters long, and are white in color.

[3][6] Pediocactus simpsonii has its flowers are grouped at the center-top of the stem and are surrounded by brown or white woolly hairs.

The outer tepals have a greenish brown stripe down the middle and have a shape like rounded rectangle but with a tapered base (oblong-cuneate).

[3] The center of the flower is filled with numerous pollen bearing filaments (stamens) that are golden yellow and 6–9 millimeters long.

The fruits are smooth, green tinged with red and filled with gray or black seeds.

[5][12] In 1893 the botanist Marcus E. Jones published a paper moving the species to genus Mammillaria, though this did not become a standard name.

The name that it is most commonly classified under as of 2023, Pediocactus simpsonii, was published by American botanists Nathaniel Lord Britton and Joseph Nelson Rose in 1913.

[2][13][14] Though this name has been well accepted since that time, 21 species or subspecies have been published that are now regarded as taxonomic synonyms of P. simpsonii, including 16 described by Fritz Hochstätter in the 1990s and 2000s.

It is also quite variable in form and bloom leading some botanists to recognize many subspecies or to confuse it with other cactuses.

[17] The species was named by Engelmann in honor of James H. Simpson, who was a surveyor and commander of the expedition to Utah in 1858–1859 where the first specimens were collected.

[23] Pediocactus simpsonii is found throughout the interior western United States from Arizona and New Mexico in the south to Idaho and Montana in the north.

In Nevada it is found in the mountain ranges of the Great Basin in the eastern side of the state.

They found it to be critically imperiled (S1) in Arizona and have not evaluated its status in Colorado or South Dakota.

[7] It is found in association with ponderosa pine forests, pinyon-juniper woodlands, cool sagebrush steppes, growing under scrub oaks, and parts of the shortgrass prairie.

It is very hardy for a cactus, one mountain valley where it grows successfully has recorded a low temperature of -47 °C.

In contrast seeds stored for several months and planted at 4.5 °C and then raised to 21 °C only showed an 18% germination rate in 2–10 weeks.