Butter! / Genesis: Provide the only available methods for getting rid of Missing No.
There is no real strategy to Missing No. as it randomizes all the player's items. The benefit of the randomization can be added by collecting more items to increase the chance of a good item synergy.
However, this item can be used to gain more health if desperately needed, as the randomization does often include items that grant you various types of hearts.
If the player has already obtained a large number of items (such as during a run where they have gained infinite money in greed mode), it is highly recommended to avoid this item, as it will almost always end up rerolling all the items the player has thus far collected into Breakfast.
Due to losing all items every level, it is beneficial to try to gain permanent stat boosts if possible. These include using pills when equipped with PHD or Virgo, sacrificing health with Potato Peeler to gain damage or Brittle Bones to gain tears, or using up Judas' Shadow.
This item is a reference to the infamous Missing No. glitch occurring in the first Pokémon games. The glitch would often corrupt save files, and therefore randomize various parts of the game as it would use the incomplete index values attributed to entities not included in the final release of the game. Isaac's appearance when affected by Missing No. is based on this glitch which could cause the player's sprite to become scrambled.
The item also resembles the painting "Composition II with Red, Blue, and Yellow" by Dutch painter Piet Mondrian.
The background color for the Missing No. achievement has the same color as all the challenge unlocks. This implies that Missing No. was originally intended to be unlocked via a challenge. (Or, perhaps, it was intended to be looked at as an error.)
The background color for the Suicide King achievement has the same color as all the boss rush unlocks. This implies that potentially Lazarus would have unlocked Suicide King for completing the Boss Rush and Suicide King (challenge #7) would have unlocked Missing No.
PS4PC FTTQ E3RZ (Secret Room directly to the right of the starting room)
PS4 X1F3 19X9 (First floor Secret Room to the left of the Shop)
PC 2QDT ALD2 (First floor Secret Room to the bottom of the Treasure Room)
PC W4Q7 JMMP (First floor Secret Room directly under the Treasure Room)
Using Glowing Hour Glass to go back to the previous floor will keep the rerolled items, which will allow to reroll them again.
Rerolling into PHD as Jacob and Esau will not reveal newly acquired pills, even if using the character that took Missing No.
Rerolling into PHD from it will not reveal newly acquired pills.