Cosmological measurements of the 21-cm line of neutral hydrogen are poised to dramatically enhance our understanding of the early universe .
In particular , both the epochs of reionization and cosmic dawn remain largely uncharted , and the 21-cm signal is one of the few probes to reach them .
The simplest 21-cm measurement is the global signal ( GS ) , which corresponds to the averaged absorption or emission of 21-cm photons across the entire sky .
While bright radio foregrounds swamp the cosmic signal over the entire frequency range observable , presenting a formidable hurdle , they can in principle be subtracted , given enough sensitivity .
Here , however , we point out an additional—and irreducible—source of uncertainty for the 21-cm GS : cosmic variance .
The cosmic-variance noise arises from the finite volume of the universe accessible to 21-cm experiments .
Due to the cosmological redshifting of 21-cm photons , each observed frequency probes our universe during a particular cosmic age , corresponding to a narrow redshift slice .
The presence of large 21-cm fluctuations makes the GS within each slice different than the GS averaged over the entire universe .
We estimate the size of this cosmic-variance noise , and find that for a standard scenario it has a size of \sim 0.1 mK , which is \sim 10 \% of the size of the expected instrumental noise of a year-long experiment .
Interestingly , cosmic variance can overtake instrumental noise for scenarios with extreme 21-cm fluctuations , such as those suggested to explain the sharpness of the claimed EDGES detection .
Moreover , as large-scale 21-cm fluctuations are coherent over long distances , cosmic variance correlates the measurements of the GS at nearby redshifts , leading to off-diagonal uncertainties that have so far been neglected .