If you can keep track of lines already read, it's trivial:

%read=();
while(defined($_=<FILE>)){
 if(!defined($read_lines{$_})){
  print OUTFILE $_;
  $read{$_}=1;
 }
}
[download]

If that's too big for your memory to hold (is it, really?), you could try to get a unique signature for each line and save that. What about an MD5 hash of it? It's 32 bites per input line, so it could be a good starting point. Beware, MD5 is not that fast if you have billions of lines!

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