Few baskets are as hit-and-miss as biotech. The group is notoriously fickle and maddeningly volatile -- and for good reason. Whims and whispers tied to the latest clinical trial results can move biotech stocks in fits and starts, making them best suited for only the most risk tolerant of investors.

However, for investors with a penchant for speculation, here are three biotechnology companies with rock-solid prospects that may make sense to include in portfolios.

Source: Gilead Sciences via Google Maps.

1. Gilead Sciences
Gilead Sciences (GILD 0.07%) has long been the dominant player in HIV treatment. The company has built a robust franchise of HIV drugs, and has increasingly discovered new ways to combine their drugs with those from competitors like Johnson & Johnson to boost market share and extend patent protection.

As a result, Gilead's product lineup includes five HIV therapies that are likely to hit billion-dollar-blockbuster sales status in 2014. That's an impressive track record all on its own, particularly considering that HIV remains underdiagnosed and undertreated globally.

But reasons to own Gilead stock stretch far beyond HIV. The company launched Sovaldi as a treatment for hepatitis C in December, and the drug has already generated more than $5 billion in sales through the first six months of 2014. Sovaldi will soon reach developing markets, where the lion's share of the 120 million plus people with hepatitis C live, thanks to a recent deal with generic drugmakers. And Gilead has a very good shot at winning FDA approval for its next-generation hepatitis C drug, which combines Sovaldi with another new Gilead drug, ledipasvir.

If that isn't enough to encourage investors to own Gilead in their portfolios, Gilead also won approval in July for its first cancer drug, Zydelig. Although Zydelig may not prove as big a blockbuster as Pharmacyclics' Imbruvica, it still marks an important entry into yet another big market.

Source: Celgene Corp

2. Celgene Corp.
Great biotech companies typically owe their greatness to one drug, and at Celgene Corp (CELG), the reason behind its top-shelf status is the blood cancer drug Revlimid. 

Revlimid first won approval in 2005 for myelodysplastic syndromes, but its label has since expanded to include use as a treatment for multiple myeloma and mantle cell lymphoma. As a result, Revlimid's sales have soared from less than $3 million in 2006 to an eyepopping $4.3 billion in 2013.

Thanks to Revlimid's success, Celgene is flush with cash, and that's allowing it to build out its product pipeline. In 2010, the company spent nearly $3 billion buying Abraxis to land Abraxane, which won approval for pancreatic cancer last fall, and could be on pace to generate a billion dollars in sales this year. More recently, the company won approval for Otezla, a treatment for proriatic arthritis that Celgene hopes will soon be used to help proriasis patients, too. And Celgene is putting big money to work investing in small, early-stage biotech companies like Epizyme, Agios, and Bluebird Bio. If any of those companies' promising drugs pay off, Celgene stands to benefit handsomely.

Source: BioMarin Pharmaceutical

3. BioMarin Pharmaceutical
Express Scripts estimates that spending on specialty medicine is heading significantly higher, as biotechs like BioMarin (BMRN -0.93%) advance high-price, targeted therapies to market. Many of this next-generation class of high-priced medicines are for orphan diseases -- those with few patients and fewer treatment options. Arguably, no one is better at bringing those therapies to commercialization than BioMarin. According to industry researcher Centerwatch, BioMarin develops drugs, and ushers them through regulators up to a year faster than many of its competitors.

Among the drugs BioMarin has successfully launched, the biggest seller is Naglazyme, an enzyme replacement therapy designed to treat Maroteaux-Lamy syndrome, a rare form of dwarfism. Sales of Naglazyme have jumped 28%, to $178 million, in the first two quarters of 2014. That's a solid showing, but Naglazyme isn't the only BioMarin drug growing quickly. All four of BioMarin's existing drugs saw sales grow double-digit percentages in the first half of the year. And, the company's most recently approved drug, Vimizim, got off to a solid start in the second quarter, too. Vimizim notched sales of $14 million in its first quarter, helping lift BioMarin's total second-quarter sales to $191.7 million, up 40% from a year ago.

The strong performance of BioMarin's orphan drug lineup is impressive, but more new drugs could be added to its portfolio soon. The company has three trials in phase 3 studies, including BMN-165 for PKU, BMN-673 for cancer in patients with BRCA gene mutation, and BMN-701 for Pompe disease.

Fool-worthy final thoughts
Biotech stocks aren't typically cheap, and these companies aren't an exception. All three trade at lofty price-to-sales ratios. Although an argument could be made that Gilead is attractively valued with a forward price-to-earnings ratio of just 11, Celgene's forward P/E is near 20. Because BioMarin is plowing so much money back into research, it doesn't even have earnings yet.

Of course, valuing biotech is always a bit tricky, and that's one of the reasons that returns in the basket tend to swing much wider than they do for the broader S&P 500. That means that, while investors are right to consider all three of these biotech companies, they should be part of a diversified portfolio.