By historical review on integrative research of syndrome differentiation and disease differentiation and considering the scientific research method of traditional Chinese medicine (TCM), the syndrome is the key subject of clinical study on TCM. During the recent 10 years or more, many new diseases and diagnostic approaches have been found and developed in Western medicine, while in TCM, the advances in research on syndrome can not keep up with the requirements of clinical practice. This problem was caused by three matters as follows: (1) Syndrome differentiation and its classification have been conservative and lack of new discovery; (2) The thinking pattern of clinical practice has been focused on disease differentiation, and only complemented by syndrome differentiation; (3) The treatment has been concentrated on the disease instead of on the syndrome. Considering these problems, the author has put forward the thinking pattern of clinical research, that is "to differentiate diseases from syndromes and to differentiate syndromes from diseases". In this way, many new syndromes and diseases will be discovered with the improvement of disease and syndrome differentiations. These advances will provide rich resources for basic theoretical and pharmacal studies of TCM, and improve the common understanding of TCM in the world.