Did your ancestor have a spouse to whom they were married for only a short time (perhaps because the spouse died young) and had no children? Have you completely researched the family of this spouse? Often the temptation is to perform little research on this "short-term" spouses, particularly when there was no issue of the marriage.
There could still be clues in the choice of this marriage partner. They could have known each other overseas, "back East," or had mutual acquaintances--all of which could be clues to tracing your actual ancestor. Just because no one descends from the "short-lived" spouse does not mean they should not be researched just as thoroughly as the spouse from which you descend.