To add to what robertes says, if you want to put the output of the program back over the input file (as you apparently do), you can use the -i flag of perl:

#!/usr/bin/perl -w -i.bak
use strict;
while (<>)              # Loop over lines of file
{ 
  next unless ($. > 2);        # Ignore first two lines
  s/do my/replacement/ if ($. == 3);
  print $_;
}
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Then you can perl edit.pl myinput, which will move the input file to myinput.bak and put the output back in myinput