Objectives Syndrome differentiation and treatment (辨證論治) is one of the core theories in Korean medicine and syndrome differentiation (辨證) constitutes a branch of disease diagnosis in Korean medicine. Yoon Gil-Young, one of the modern outstanding scholar of basic medical science in Korean medicine, wrote on basic theories of Korean medicine such as physiology, pathology, formula science, etc. Hereby we will analyze and discuss his works to understand his recognition of historical changes in the syndrome differentiation. Methods We conducted researches into the two works of Yoon Gil-Young's, which are "The Clinical Formula Science of Eastern Medicine (東醫臨床方劑學)" and "The theory of Four-Constitution Medicine (四象體質醫學論)". From Yoon's academic standpoint which connects the basic medical science with the clinical medicine, we analyzed his opinion about syndrome differentiation and its historical changes. Results According to Yoon's research work on syndrome differentiation and its historical changes, the development of syndrome differentiation, which goes in harmony with the history of Korean medicine, has its deep root in " Huangdi's Internal Classic (黃帝內經)" and "Treatise on Cold Damage and Miscellaneous Diseases (傷寒雜病論)". And through "Treatise on the Spleen and Stomach (脾胃論)" and the articles of warm disease (溫病論), the theory of syndrome differentiation became extended to the whole clinical diagnostic field in Korean medicine, finally including the achievements in "Treasured Mirror of Eastern Medicine (東醫寶鑑)", "Longevity and Life Preservation in Eastern Medicine (東醫壽世保元)". Conclusions Yoon Gil-Young recognized that the system of syndrome differentiation was developed in accordance with the theories from the "Treatise on Cold Damage and Miscellaneous Diseases", then the "Treatise on the Spleen and Stomach" and the articles of warm disease. The four-constitution medicine in Korea and Koho school in Japan which lays emphasis on abdominal signs also contributed to its development. Syndrome differentiation can be categorized basically into three states of intrinsic cold (本寒), intrinsic deficiency (本虛), intrinsic heat (本熱) according to the deficiency and excess in human body metabolism.