Darwin introduced the concept that random variation generates new living forms. In this paper, we elaborate on Darwin's notion of random variation to propose that biological variation should be given the status of a fundamental theoretical principle in biology. We state that biological objects such as organisms are specific objects. Specific objects are special in that they are qualitatively di↵erent from each other. They can undergo unpredictable qualitative changes, some of which are not defined before they happen. We express the principle of variation in terms of symmetry changes, where symmetries underlie the theoretical determination of the object. We contrast the biological situation with the physical situation, where objects are generic (that is, di↵erent objects can be assumed to be identical) and evolve in well-defined state spaces. We derive several implications of the principle of variation, in particular, biological objects show randomness, historicity and contextuality. We elaborate on the articulation between this principle and the two other principles proposed in this special issue: the principle of default state and the principle of organization.