Knudson performed a statistical analysis on cases of retinoblastoma, a malignant tumor of the retina that occurs both as an inherited disease and sporadically.
In addition, the children with inherited retinoblastoma often developed the tumor in both eyes, suggesting an underlying predisposition.
In non-inherited retinoblastoma, instead two mutations, or "hits", had to take place before a tumor could develop, explaining the later onset.
An inactivation of both alleles is required, as a single functional tumor suppressor gene is usually sufficient.
Under this model, cancer arises as the result of a single, isolated event, rather than the slow accumulation of multiple mutations.