But S&P 500 are not the 500 companies with highest revenue. Its 500 companies selected by a committee to be representative of the american economy. Its not as biased as you suggest.
My bad, but I think the study would have actually been less flawed with the Fortune 500. S&P are subjectively chosen "market leaders"; thus you not only get the bias towards companies with large revenues, but also an opaque bias related to the committees non-transparent criteria.
The stocks included in the S&P 500 are those of large publicly held companies that trade on either of the two largest American stock market exchanges; the New York Stock Exchange and the NASDAQ. Wikipedia
I agree that companies with 3-100 employees will just not appear in SP500.
However, Mercury Interactive was included when it had around 1000 employees. 1000 is a lot, but you can still learn by comparing a company with 1000 employees to HP with 300,000.
http://en.wikipedia.org/wiki/S%26P_500#Selection