Whenever Isaac clears a room, has a chance to open a neighboring Red Room.
This effect can occur while Isaac is inside a Red Room, but the chance is smaller.
Notes
It's possible to increase the chance of a Red Room unlocking if multiple Crystal Keys are held, e.g. from absorbing using Smelter, holding Mom's Box, having a golden Crystal Key. The chance for a Red Room door to unlock depends on the number of Crystal Keys held and if the room cleared is normal or Red.
Crystal Key Count
Normal Room
Red room
1
33.3%
12.5%
2
50%
16.6%
3
100%
25%
4
100%
50%
5
100%
100%
Each cleared wave of a Challenge Room has a chance to generate an adjacent Red Room.
Rooms that are re-fought using the D7 have a chance to generate additional Red Rooms.
Doors do not have to open to an actual valid Red Room, and can lead outside the map and into an I AM ERROR Room.
Red Room.
Smelter, holding 
Mom's Box, having a golden Crystal Key. The chance for a Red Room door to unlock depends on the number of Crystal Keys held and if the room cleared is normal or Red.
Challenge Room has a chance to generate an adjacent Red Room.
D7 have a chance to generate additional Red Rooms.
I AM ERROR Room.
Keys 
Tainted Lost Unlocks 
Mother Unlocks 
The Binding of Isaac: Rebirth
