From the 15th century to the present a number of critical developments provide the theoretical foundation to make unbiased estimates of the four first-order stereological parameters: number (N), volume (V), surface area (S), and length (L).

• In 1635, Buonaventura Cavalieri showed that the mean volume of a population of non-classically-shaped objects can be estimated in a theoretically unbiased manner from the sum of areas cut through the objects.

Cavalieri's method allows for the morphological estimation of total volume of any population of objects from the area on a systematic-random sampling of sections through the objects.

• In 1777, the naturalist George Leclerc Buffon presented the Royal Academy of Sciences in Paris with the needle problem.

Buffon had a strong interest in the laws of probability. His needle problem showed that a needle tossed at random onto a grid of lines intersects each line with a probability directly proportional to the length of the needle, with no further assumptions. Buffon's needle problem provided the theoretical basis for estimating the total length and total surface area of non-classically shaped objects.

• In 1847, the French mining engineer and geologist Auguste Delesse showed that the profile area of a random section through a population of objects is proportional to the expected value of the objects' volume.

Delesse was interested in quantifying the various phases of mineral deposits in rocks, specifically the quantitative relationship between the phase area on the cut surface of a rock and the total phase volume in the entire rock. By comparing the area of mineral phases on cut surfaces with the total phase volume in the whole specimen, Delesse showed that the total area of a phase on each cut surface is proportional to the total phase in the entire specimen. Today, the Delesse principle provides the basis for estimating the volume of non-classically shaped objects based on their profile areas on random sections.

• In 1925 Swedish mathematician S.D. Wicksell described the corpuscle problem to explain why accurate estimates of object number cannot be obtained from profile counts on single, thin histological sections.

Wicksell wanted to know the number of thyroid globules in the thyroid gland. From sections cut through the thyroid and carefully reconstructed in 3-D, he showed that the number of globules in given volume of tissue the number per unit volume, Nv, cannot be estimated from the number of globule profiles on the cut surface of sections, NA. Since then numerous failed attempts have sought to overcome the corpuscle problem using "correction formula", which simply add further bias through assumptions and models that do not apply to biological objects.

• In 1984 D.C. Sterio published the disector principle, the first unbiased method for estimating the true number of objects in given volume of tissue, Nv.

D.C. Sterio is the pseudonym of a well-known Danish stereologist. The disector method was designed to overcome the corpuscle problem without assumptions, models, or correction factors. The method D.C. Sterio developed requires two virtual planes, a "disector-pair", an unbiased counting frame, and unbiased counting rules to count the number of objects per unit volume, without assumptions about the size, shape, and orientation of the objects of interest.

With the advent of the disector principle, stereologists realized that quantitative methods of morphological analysis could in theory overcome the most severe forms of bias introduced by cutting 3-D objects into 2-D sections.