The smallest 6-digit number is 100000, and the greatest 4-digit number is 9999. To find the difference between these two numbers, we simply need to subtract the greatest 4-digit number from the smallest 6-digit number.
So, the calculation would look like this:
100000 - 9999 = 90001
Therefore, the difference between the smallest 6-digit number and the greatest 4-digit number is 90001.