The most important issue.

We now use this phrase as part of 'an eye for the main chance', referring to someone who is ambitious and eager to promote their own advancement. The first known use of it in print is in John Lyly's, Euphues, the anatomy of wyt, 1579:

"Either content yourself with my choice, or lette mee stande to the maine chaunce."

Shakespeare used it soon afterwards in Henry VI Part 2, 1597:

WARWICK:

There is a history in all men's lives,
Figuring the nature of the times deceased;
The which observed, a man may prophesy,
With a near aim, of the main chance of things
As yet not come to life, which in their seeds
And weak beginnings lie intreasured.
Such things become the hatch and brood of time;
And by the necessary form of this
King Richard might create a perfect guess
That great Northumberland, then false to him,
Would of that seed grow to a greater falseness;
Which should not find a ground to root upon,
Unless on you.