As some reviewers have already mentioned, this book is hard to ascribe to any one genre. I wouldn't call it truly science fiction, but neither would I call it horror, as some have. And it doesn't truly fit the mold for fantasy. I would argue that is has elements of all three. One reviewer described it as speculative fiction.
Either way, to the story itself. This is a story about four college buddies and roomates (a Jew, a jock, a rich kid and a homosexual) on a road trip across the country in hopes of finding immortality. The trip is all based on a manuscript, the Book of Skulls, one of them, Eli, found and translated in the library. They are seeking the Brotherhood of the Skull monastery, which is reportedly located just outside Pheonix, Arizona. The idea is that a group of four is required, but the catch is one must commit suicide and one must be murdered in order for the other two to attain immortality.
The story is told as quick snippets from the viewpoint of each of the four main protagonists. For some reason, I really liked this style of storytelling although the story wasn't what I was expecting. Up until the end the story was all about the soul searching spiritual journey of the four protagonists. There was a surprise ending to the story, at least to me.