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Healthcare stocks are among the most heavily shorted stocks on the market and the number of shares held short relative to shares outstanding for these three companies is downright stratospheric.

Because sky-high short interest can either indicate that a company is ripe for a big fall or about to benefit from a short squeeze that can send shares soaring, let's take a closer look at these three companies and see if investors are right to be selling these stocks short.

No. 1: Athenahealth (NASDAQ:ATHN)
Despite delivering revenue growth of 24% last quarter and offering up a forecast suggesting that full year bottom line results will exceed guidance issued earlier this year, a staggering 29.24% of athenahealth's shares outstanding are sold short by investors, including billionaire hedge fund manager David Einhorn.

At the May 2014 Sohn Investment Conference, Einhorn called out athenahealth as one of his top stocks to short because, in his view, it is part of a "narrow group of cool kid stocks [that] have disconnected from traditional valuations and formed a bubble." 

Einhorn reiterated that opinion earlier this year, but since Einhorn's worries stem from valuation, rather than a failure of athenahealth's business model, investors might want to think twice before joining him in betting against this company.

Athenahealth's sales and profit are growing rapidly thanks the ongoing electrification of doctors offices and if Einhorn covers his stake in athenahealth, it could be months before investors find out.

Of course, no one knows when Einhorn will cover, but athenahealth's recent financials show that its business isn't slowing. The company expects to deliver sales at the midpoint of its previously announced full year guidance of between $905 million to $925 million and non-GAAP EPS that exceeds the top end of its projected range of between $1.10 and $1.20. If so, then 2015 will continue a string of growing sales and profit that has led to a more than tripling of revenue since 2010.  

ATHN Revenue (Annual) Chart

ATHN Revenue (Annual) data by YCharts

Admittedly, athenahealth's growth has yet to rein in its valuation and that remains the biggest, if only, reason to stay short its shares. However, its ongoing earnings growth, robust gross margins of 62.9%, and a huge market opportunity make this one stock that I'd rather own than be short.

No. 2: Ziopharm Oncology (NASDAQ:ZIOP)
There's little doubt that advances in gene technology are allowing drugmakers to make big leaps forward in cancer treatment and Ziopharm's attempts to re-engineer the immune system to more easily find and destroy cancer cells is one of the most intriguing of these advances.

The ability to superpower T-cells so that they bind to proteins expressed on cancer cells could reduce or eliminate the need for toxic chemotherapy, yet sellers are holding 26.5% of Ziopharm Oncology's shares short.

Short sellers pessimism is understandable. Historically, over 90% of cancer drugs entering human trials fail and since Ziopharm Oncology's drugs are in the earliest stages of clinical research, a lot can go wrong from here. If it does, then Ziopharm could find itself in a tough spot because its costs are surging. In Q3, Ziopharm's research and development expenses jumped to $17 million from $9.7 million a year ago and as a result, Ziopharm posted a net loss of $18.2 million.

Nevertheless, Ziopharm Oncology expects to release a flurry of data in the coming year that could make shares pop or drop. The company expects to report data from early stage studies of its Ad-RTS-hIL-12 therapy for breast cancer and brain cancer and to update progress on its various T-cell approaches by the end of this year. Since shares could move violently up, or down, depending on those presentations, I'd rather sit on the sidelines than be long or short this stock.

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Source: Exelixis

No. 3: Exelixis (NASDAQ:EXEL)
Exelixis' only approved drug is Cometriq, which is approved to treat medullary thyroid cancer, or MTC, a rare cancer affecting about 1,200 people in the United States. 

Because the MTC market is small, Cometriq's sales totaled just $25 million last year and therefore investors need Exelixis to either win approval for Cometriq's use in other indications or to launch other new drugs to justify its billion dollar plus market cap.

Last year, those who sold Exelixis shares short were rewarded hansomely when Cometriq's prostate cancer trial didn't pan out and Exelixis shares dropped to less than $1.50 from a high of over $8.

This year, short sellers have endured a punishing quadrupling in Exelixis' shares tied to renewed enthusiasm surrounding Cometriq's potential in kidney cancer and Exelixis' cobimetinib in metastatic melanoma.

In October, Exelixis filed an application for approval of Cometriq for use in kidney cancer that clears the way to an FDA decision next year, and on Nov. 10, the FDA approved cobimetinib, or Cotellic, for use in melanoma patients that are BRAF gene positive.

Although those are positive developments that could jump-start Exelixis revenue in 2016, short sellers remain short 26.4% of Exelixis shares.

Sellers skepticism could stem from the fact that new therapies in development for melanoma and kidney cancer could crimp the market potential for Exelixis.

Or perhaps its over lingering concerns regarding Exelixis financials. In the third quarter, Exelixis lost a whopping $47.6 million and that means it needs a lot of things to go its way if it wants to turn profitable anytime soon.

Overall, Exelixis recent run higher means its $1.3 billion market cap is at levels that already reflect the positive impact of both Cometriq and Cotellic and given that Exelixis has $371 million in long-term debt, I think a good argument can be made that this stock is a bit ahead of itself and that it may need to digest some of its big move higher. 

Todd Campbell has no position in any stocks mentioned. Todd owns E.B. Capital Markets, LLC. E.B. Capital's clients may have positions in the companies mentioned. The Motley Fool recommends Athenahealth and Exelixis. Try any of our Foolish newsletter services free for 30 days. We Fools may not all hold the same opinions, but we all believe that considering a diverse range of insights makes us better investors. The Motley Fool has a disclosure policy.