Open two instances of Notepad++

Hit Alt+F6. This opens the current tab in a new window.

If you don't feel keyboard-y, going to Run, Open in another instance has the same effect.

Other than opening another instance with Alt+F6 (as in @qweet's answer), if you already have the file open in the first instance of Notepad++, here are some alternatives:

• Click on the tab for the file and then drag it outside the Notepad++ window and drop it anywhere outside; this will open a new instance with the desired file. For this to work, the first instance should not be maximized so that you have space to drop the tab outside of the window.
• Right-click on the tab for the file and choose one of the following options:
  • Move to new instance: opens new window with the file in it; removes file from original instance.
  • Open in new instance: opens new window with the file in it; retains same file in the original instance.
  • Move/Clone to other view: opens split window in the same instance with the file in the split window.

The advantage of all of these approaches is that the new instance already includes the file that you had open in the original instance.