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The Cockroach Queen is the fourth boss in Duke Nukem: Manhattan Project. She appears in the third part of the fourth chapter "Unholy Underworld". She is a gigantic mutated cockroach and ranks among the biggest bosses. She has good close combat abilities, the ability to spit G.L.O.P.P. and the strength to easily knock carriages off the track. Duke has to keep his distance as she easily outclasses him in melee.
When Duke walks through the red key door towards the end of the third part of Unholy Underworld, he will come face to face with the Cockroach Queen.
The battle begins with Duke under some wooden scaffolding, and the Queen further away from him to the right. She attacks Duke by throwing rocks at him. When Duke deals enough damage to her; the cave Duke is fighting her in will begin to collapse and the a boulder will fall on top of the Queen. Duke then activates a nearby train to escape the area remarking "Ah, just in time." only to quickly correct himself by saying "Maybe I spoke too soon." when the Queen is revealed to still be alive and begins chasing the train.
Duke begins the second battle on the last carriage with the Queen trying to attack him with her claws and by spitting G.L.O.P.P. at him. After doing enough damage the camera will zoom backwards, showing the Queen catching up to the carriage Duke's currently on; Duke must jump to the next carriage, otherwise he will die because the Queen will knock the carriage off the track. This process will repeat for each carriage, until the Queen has lost enough health, then she runs in front of the final carriage with Duke remarking "Looks like you've gotten ahead of yourself there." Before impact, Duke jumps off the train and the Queen is smashed against the wall at the end of the line and explodes into pieces; ending her threat for good.
- Aside from the encounters with Mech Morphix, the Cockroach Queen is the only boss to actually have an appearance and abilities unique to herself as every other boss in Duke Nukem: Manhattan Project is a stronger version of a common enemy Duke will encounter throughout the game.
- Aside from Morphix, she's the only boss Duke has to fight more than once as every other boss is killed after the first battle.