The main conflict in the story stems from the fact that Wing Biddlebaum is different.  He is a man who by nature expresses himself with his hands, and because of this, he is vilified and misunderstood.  The fact that he is even a resident of Winesburg, Ohio is because of the extreme conflict caused by his hands at his former place of residence in Pennsylvania.  He had been a gifted schoolteacher, but his habit of touching his students when he spoke was interpreted to have sexual connotations, and in the resulting hysteria, he was banished from the town.

Biddlebaum's hands cause conflict within himself.  Ironically, he does not understand why his hands are looked upon as a problem by others, and so he becomes reclusive, and lives a life in isolation.  The only person who has been able to penetrate his protective shell is George Willard, but when Biddlebaum tries to communicate with him, he finds his hands reaching out to touch him of their own accord, and, in horror, he pulls away.

George Willard perceives that Biddlebaum's "hands have something to do with his fear of...everyone", but, "touched by the memory of the terror...in the man's eyes", he dares not ask about them.  The conflict Willard feels about bringing up the subject of the man's hands prevents the tow of them from establishing true communication.

Among the other ironies in the story are the fact that Biddlebaum's dexterity with his hands brings him fame in Winesburg, but it also marks him as different, and as such keeps him isolated from others.