Gallbladder cancer is a relatively rare form of malignancy about which our knowledge is scant. However, a unique combination of predisposing factors - including genetic predisposition, geographic distribution, female gender bias, chronic inflammation and congenital developmental abnormalities - makes this type of cancer unique and offers potential for understanding cancer pathogenesis in general. An understanding of how these risk factors contribute to the molecular basis of the disease is essential for understanding the origins of this unusual cancer.