
Question mark = possible ultra secret room location. Dark red square = red room near a regular room. Bright red square = red room near a special room. Obviously, there are many more possibilities, but these are going to be the most common: The Binding of Isaac: Rebirth How to Find Ultra Secret Rooms Here are some useful examples of valid and invalid locations of ultra secret rooms. If the level generation works as intended, you will only need to create one red room to find the ultra secret room, as it is revealed immediately after you open the neighboring red room. The level usually has 3+ possible spots for an ultra secret room, but if there aren’t any valid spots for these rules to apply, the second rule will be disregarded. Both of these red rooms must be connected to at least one non-red room (but it cannot be the same one if it’s the only non-red room both red rooms border with). At least one of these red rooms must be connected to any special room (treasure room, shop, arcade, regular or super secret room etc)besides a boss room.
Under normal circumstances, an ultra secret room will be generated between 2 (sometimes more) red rooms. Since red rooms cannot be created in greed mode, ultra secret rooms are limited to regular runs.
The Crystal Key trinket opens red rooms too, but you can’t control it so it won’t be very helpful here. Obviously, the most reliable one the Red Key, but you can also use Cracked Key or Soul of Cain. In order to find an ultra secret room, you will need an item/consumable capable of creating red rooms. This can be circumvented if you have a trinket that allows those rooms to spawn on late-game floors, like the Wicked Crown or Silver Dollar.