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Microwaved rat
In Chapter 2: 'Damn! It's Late...', there is a room with a microwave. Directly under the microwave is a cupboard that can be opened to find a rat. You can pick up the rat and put it in the microwave.
Notice: This room is also shared with the Duke Nukem Fanboy.
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300 reference
Duke will say 'Tonight, you dine in Hell' after a kill in the 'Vegas In Ruins' chapter. This is a reference to 300, when Leonidas says 'Tonight, we dine in Hell!'
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Easy 'I Need A Date' achievement
In 'The Shrunk Machine' chapter, near the beginning, after entering the first large room, straight ahead across the room are some double doors. There is a calendar on the wall behind the double doors. Look at all pages to get the 'I Need A Date' achievement. There is another calendar in Part 2 of 'The Forkstop' chapter on the wall in one of the rooms.
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Overdrive mode
Reach Level 40 in Multiplayer mode to unlock Overdrive mode. In this mode, all points earned are doubled with the exception of challenges. You will also get 20 points each time an enemy is damaged.
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Christian Bale reference
In Chapter 2: 'Damn! It's Late...', after walking off the set, you will see an actor yelling at someone. He says things like 'Do you want me to trash your mics? DO YOU?' and 'You're a nice guy, you really are but you're a f**king amateur'. This is a reference to when Christian Bale freaked out on the set of Terminator: Salvation.
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Activate Cheats
Successfully complete the game on the indicated difficulty to unlock the corresponding cheats and bonuses at the 'Extras' menu.
Notice: Enabling the 'Infinite Ammo', 'Instagib', or 'Invincibility' cheat options will prevent Ego points and achievements from being earned.
| Duke Sound Board | Easy difficulty or higher |
| Development Timeline | Easy difficulty or higher |
| Grayscale Mode (black and white graphics) | Normal difficulty or higher |
| Screenshots | Easy difficulty or higher |
| Game Speed (adjust game speed) | Normal difficulty or higher |
| Mirror Mode (graphics are mirrored horizontally) | Normal difficulty or higher |
| Infinite Ammo | Normal difficulty or higher |
| Concept Arts | Easy difficulty or higher |
| Movies | Easy difficulty or higher |
| Duke 3D Freeze Ray (freeze ray fires bouncing ice projectiles) | Normal difficulty or higher |
| Instagib (enemies killed with one shot and always gib) | Normal difficulty or higher |
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| Invincibility (no damage from bullets or explosions) | Normal difficulty or higher |
| Head Scale (adjust head size of enemies and NPCs) | Easy difficulty or higher |
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| Triptych Office Photos | Easy difficulty or higher |
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Dead Space reference
In 'The Hive' chapter, after you tickle the first door, turn to your left, and walk forward. Crouch to get under the bridge, and you will see a dead EDF Soldier with Isaac Clarke's signature engineer helmet.
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Easy 'Air-Duke' achievement
In the 'Duke Nukem's Titty City' chapter, go to the game room at the back of the club, and play a game of air hockey. Instead of focusing on scoring, try defending your goal as good as possible. The rest will happen by accident since the opponent is very weak.
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Mortal Kombat reference
In the Duke Nukem soundboard, there is an entry called 'Fatality'. When you select it, Duke says 'Duke wins, Fatality.'
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Tommy Tutone reference
In the bathroom in the 'Duke Nukem's Titty City' chapter, above one of the urinals is some grafitti that reads 'Jenny - 867-5309'. This is a reference to the Tommy Tutone song of the same name.
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Achievements
Do the following things to obtain the corresponding Gamerscore points:
| 5 Points |
| Juiced | Take steroids in SP. | | | Nobody Likes a Whiner | Knock out the talent at the talk show. | | | He's Got a Hologram! | Use a Holoduke in SP. | | | Flagon of Chuckles | Drink a beer in SP. | | | Special Thanks | Watch the credits all the way through. | | | I Need a Date | Look at every page of a calendar in SP. | | | Sunday, Black Sunday | Shoot down the blimp above the stadium. | | | 10 Points | | Big Guns, Big Ships | Blow up 5 enemy gunships or dropships. | | | Substance Abuser | Drink beer while on steroids or vice versa in SP. | | | Party Animal | Drink all of the beers in the strip club. | | | Companion Barrel | Unlock the secret closet at the end of the Forkstop. | | | I Need a Towel | Get hit by 10 Pregnator bombs. | | | FBT | Get knocked down 10 times. | | | Sticky Bomb Like You! | Put a Trip Mine on a live alien. | | | One-Eyed Freak | Overcome the Cycloid. | | | Turd Burglar | Find and steal a piece of poo. | | | Natural Disaster 3x | Kill 3 aliens at once. | | | Fork the Pork | Kill 6 aliens with the forklift. | | | Noms | Eat 10 pieces of food during the SP campaign. | | | Pescaphobe | Kill all the catfish in the underwater level. | | | Drawrings | Doodle something on the whiteboard in SP. | | | 15 Points | | Dead Useful | Kill 10 aliens with environmental explosives. | | | Downtown Barrel Cleardown | Kill 10 aliens with tossed objects. | | | 20 Points | | Road Rage | Kill 15 aliens with the monster truck. | | | Freeze Well! | Kill 15 frozen aliens. | | | Duke Angry, Duke Smash! | Kill 15 aliens with melee attacks while on steroids. | | | Hippy-Stomper | Foot stomp 12 aliens. | | | Piece of Cake | Finish the SP campaign on Easy Difficulty. | | | Baron von Nukem | Shoot down 20 alien fighters. | | | Judge, Jury, Executioner | Execute 20 aliens. | | | Trapper | Kill 10 aliens with Trip Mines. | | | 25 Points | | Balls of Steel | Gain a 1,000,000 pinball score in SP. | | | Extermination | Kill 50 aliens. | | | Octacide | Overcome the Octaking. | | | Call Waiting | Listen to all phone messages. | | | On the Noggin | Kill 30 aliens with headshots. | | | A Good Dam Fight | Overcome the Battlelord on the Hoover Dam. | | | Pit Champion | Overcome the Battlelord in Las Vegas. | | | Lots of Whacking | Be victorious in a game of Alien Abortion in the strip club. | | | 30 Points | | Bucket Head | Find all 3 helmets in the SP campaign. | | | Let's Rock | Finish the SP campaign on Normal Difficulty. | | | Air-Duke | Be victorious in air hockey with a score of 7-0 in the strip club. | | | 35 Points | | Clearing the One-Eyed Worm | Overcome the Energy Leech. | | | 40 Points | | I Am All That Is Man | Discover all Ego cap awards. | | | Annihilation | Kill 100 aliens. | | | Come Get Some | Finish the SP campaign on Hard Difficulty. | | | Not Bad for a Human | Overcome the Alien Queen. | | | 50 Points | | Nuclear Devastation | Kill 250 aliens. | | | Gunslinger | Carry the gold pistol through the whole SP campaign. | | | Damn, I'm Good | Finish the SP campaign on Insane Difficulty. | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
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Easy 'Sticky Bomb Like You!' achievement
At the beginning of 'The Duke Dome' chapter, you will get an infinite amount of explosives when entering a building. Throw a trip mine directly on one of the enemies to get the 'Sticky Bomb Like You!' achievement.
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Bonus accessories
Successfully complete the indicated multiplayer weapon challenge to unlock the corresponding accessory in the changing room:
| Cheese Hat | Get 250 kills with the Ripper (Swiss Cheese III). |
| Brain Sucker | Get 250 kills with the Enforcer (Laser Seeking Missiles III). |
| I Shot Stupid Logo | Get 250 kills with the Railgun (Right In The Eye III). |
| Baseball Cap | Get 75 kills with pipe bombs (Splatter King III). |
| Wolf Logo | Get 75 kills with Steroids (Roid Rage III). |
| Detonator Logo | Get 250 kills with the Rocket Launcher (Boom Goes The Weasel III). |
| Tie-Dye Shirt | Get 250 kills with the AT laser (Medium Rare III). |
| Military Hat | Get 250 kills with the Pistol (Size Doesn't Matter III). |
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| Uncle Sam Hat | Stomp on 75 enemies (Pee Wee Vermin III). |
| Canadian Flag Logo | Get 75 kills with the Garter Pistol (Tiny But Deadly III). |
| Retro Duke Logo | Get 250 kills with the Devestator (Meat Grinder III). |
| Backwards Baseball Cap | Get 250 kills with the Shotgun (Burger Face III). |
| Ski Goggles | Execute a frozen player 75 times (Ice To See You III). |
| Hoplite Helmet | Get 75 melee kills (Punchy McPuncher III). |
| Jester Hat | Get 75 kills with trip mines (Watch Your Step III). |
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| WTF Logo | Get 75 kills with exploding barrels (Smile You Son Of A Bitch III). |
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Starship Troopers reference
After killing some enemies, you will hear Duke say 'I'm from Las Vegas, and I say kill 'em all!'. This is a reference to Starship Troopers when Johnny Rico says 'I'm from Buenos Aires, and I say kill 'em all!'.
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Easy 'Turd Burglar' achievement
Poop can be found in toilets. There is some poop in the toilets in the room where the game begins ('Duke Lives' chapter). Grab poop from a toilet and throw it to get the 'Turd Burglar' achievement.
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Easy 'Sunday, Black Sunday' achievement
In the 'Duke Lives' chapter, at the very beginning of your first fight, you will see a blimp in the background. Keep shooting it until you get the 'Sunday, Black Sunday' achievement.
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Halo reference
At the begin of the 'Vegas In Ruins' chapter, before you enter the building, there is a van with weapons. The armor in the van is the same from Halo, other than the Nukem insignia on the helmet visor.
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Inception reference
In the 'Duke Nukem's Titty City' chapter, enter the room where you can microwave the popcorn. Look on the desk where you can use the security camera, and you will see a spinning top, like the one Leonardo DiCaprio uses in Inception.