It is distinct from the short-tailed weasel (Mustela erminea), also known as a "stoat", a close relation in the genus Mustela that originated in Eurasia and crossed into North America some half million years ago; the two species are visually similar, especially the black tail tip.

[3][4] In 1993, the classification, Mustela frenata, was accepted into the second edition of the Mammal species of the world: a taxonomic and geographic reference, which was published by the Smithsonian Institution Press.

[5] The long-tailed weasel is the product of a process begun 5–7 million years ago, when northern forests were replaced by open grassland, thus prompting an explosive evolution of small, burrowing rodents.

The long-tailed weasel's ancestors were larger than the current form, and underwent a reduction in size to exploit the new food source.

The long-tailed weasel arose in North America 2 million years ago, shortly before the stoat evolved as its mirror image in Eurasia.

The species thrived during the Ice Age, as its small size and long body allowed it to easily operate beneath snow, as well as hunt in burrows.

[9] The eyes are black in daylight, but glow bright emerald green when caught in a spotlight at night.

In northern areas in winter, the long-tailed weasel's fur becomes white, sometimes with yellow tints, but the tail retains its black tip.

[8] The long-tailed weasel has well-developed anal scent glands, which produce a strong and musky odour.

[11] Unlike skunks, which spray their musk, the long-tailed weasel drags and rubs its body over surfaces in order to leave the scent,[12] to mark their territory and, when startled or threatened, to discourage predators.

[17] The long-tailed weasel mates in July–August, with implantation of the fertilized egg on the uterine wall being delayed until about March.

The kits are born partially naked, blind and weighing 3 grams (0.11 oz), about the same weight of a hummingbird.

The long-tailed weasel's growth rate is rapid, as by the age of three weeks, the kits are well furred, can crawl outside the nest and eat meat.

Weaning begins at this stage, with the kits emerging from the nest and accompanying the mother in hunting trips a week later.

Another common defense of long-tailed weasels is its black-tipped tail, which differs in color from the rest of the body.

[22] The long-tailed weasel is an obligate carnivore which prefers its prey to be fresh or alive, eating only the carrion stored within its burrows.

Its primary prey consists of mice, rats, squirrels, chipmunks, shrews, moles and rabbits.

noveboracensis (DeKay, 1840) perdus (Merriam, 1902) richardsoni (Bonaparte, 1838) In North America, Native Americans (in the region of Chatham County, North Carolina) deemed the long-tailed weasel to be a bad sign; crossing its path meant a "speedy death".