Although there are nine known isotopes of helium (₂He) (standard atomic weight: 4.002602(2)), only helium-3 (³
He
) and helium-4 (⁴
He
) are stable. All radioisotopes are short-lived, the longest-lived being ⁶
He
with a half-life of 806.92(24) milliseconds. The least stable is ¹⁰
He
, with a half-life of 260(40) yoctoseconds (2.6(4)×10⁻²² s), although it is possible that ²
He
may have an even shorter half-life.

In the Earth's atmosphere, the ratio of ³
He
to ⁴
He
is 1.343(13)×10⁻⁶. However, the isotopic abundance of helium varies greatly depending on its origin. In the Local Interstellar Cloud, the proportion of ³
He
to ⁴
He
is 1.62(29)×10⁻⁴, which is 121(22) times higher than that of atmospheric helium. Rocks from the Earth's crust have isotope ratios varying by as much as a factor of ten; this is used in geology to investigate the origin of rocks and the composition of the Earth's mantle. The different formation processes of the two stable isotopes of helium produce the differing isotope abundances.

Equal mixtures of liquid ³
He
and ⁴
He
below 0.8 K separate into two immiscible phases due to differences in quantum statistics: ⁴
He
atoms are bosons while ³
He
atoms are fermions. Dilution refrigerators take advantage of the immiscibility of these two isotopes to achieve temperatures of a few millikelvins.