In Generation II, Cerulean and Fuchsia City didn't use their music from Generation I, and shared themes with Celadon City and Viridian City, respectively. However, when remade, Cerulean and Fuchsia were given their Generation I theme again, but because they didn't have this theme in Generation II, when using the GB Sounds, an original Generation II-styled remix was used.

HeartGold and SoulSilver include the Champions from each of the previous paired versions: Blue from Red and Green, Lance from Gold and Silver, Steven Stone from Ruby and Sapphire, and Cynthia from Diamond and Pearl.

If you interact with your Snorlax in Mt. Silver in the game, it will say; "SNORLAX is feeling very eager". This is due to Red in Mt. Silver also owning a Snorlax. Unique messages will also appear if you interact with Pikachu or Charizard.

The Kimono Girls' dance to summon a member of the tower duo primarily consists of circular motions. In HeartGold, they move clockwise, and in SoulSilver, they move counter-clockwise.

The Togepi that hatches from the egg given to the player by Professor Elm has the egg move Extrasensory. This means that the Togepi's father was either a Hoothoot or a Noctowl.

When you team up with Lance in the Rocket HQ. He has a LVL.40 Dragonite which is 15 levels lower that what it should be. Also, when you fight him for the first time as champion, his three Dragonites are a few levels lower. This also happened in the Game Boy versions.

These 2 games mark the first time that the English versions were announced before the games were released in Japan.

If the game detects that it is being played on a flash cart or emulator, it will freeze at the beginning of a battle with the player's Pokeballs spinning constantly.

There's an item named 'GB sounds' which stands for Game Boy sounds, and is only obtainable after you beat all 16 gym leaders. Despite the fact that the GB Sounds is supposed to sound like the original music from the Game Boy and Game Boy Color, none of the songs sound exactly like the originals. The reason that GB Sounds doesn't perfectly emulate the original soundtrack is due to the games using a sound font for MIDI playback, rather than generating real 8-bit chiptune sounds.