[7] In 1815, the Edinburgh Review contained an article on the system of "craniology" devised by Franz Joseph Gall and Johann Gaspar Spurzheim, denouncing it as "a piece of thorough quackery from beginning to end".

On investigating the subject for himself, he became satisfied that the fundamental principles of phrenology were true: "that the brain is the organ of mind; that the brain is an aggregate of several parts, each subserving a distinct mental faculty; and that the size of the cerebral organ is, caeteris paribus, an index of power or energy of function.

The sharp controversy included challenges to public disputes and mutual charges of misrepresentation, in which Spurzheim took part.

[9] In 1836, Combe stood for the chair of Logic at the University of Edinburgh against two other candidates: Sir William Hamilton and Isaac Taylor.

[12] He helped to set up a school in Edinburgh run on the principles of William Ellis, and did some teaching there in phrenology and physiology.

He and William A. F. Browne opened a debate on introducing humane treatment of psychiatric patients in publicly funded asylums.

[17][18] In 1842, Combe gave a course of 22 lectures on phrenology at the Ruprecht Karl University of Heidelberg and travelled about Europe enquiring into management of schools, prisons and asylums.

[8] He argued in it: "Mental qualities are determined by the size, form and constitution of the brain; and these are transmitted by hereditary descent."

Combe was one of an active Edinburgh scene of people thinking about the nature of heredity and its possible malleability, as Lamarck proposed.

Combe himself was no Lamarckian, but in the decades before Darwin's Origin of Species was published, the Constitution was probably the single most important vehicle for disseminating naturalistic progressivism in the English-speaking world.

[20] Combe's 1838 Answers to the Objections Urged Against Phrenology was followed in 1840 by Moral Philosophy and in 1841 by Notes on the United States of North America.