Immunohistochemical evaluation of hormone receptors for breast cancer has been performed parallel to biochemical assays. Recently, immunohistochemistry has tended to substitute the biochemical method in Japan. To clarify the factors concerned and problems to be resolved, we reviewed our evaluation system for hormone receptors by immunohistochemistry from 1990. A total of 861 breast cancer samples were examined by immunohistochemistry and biochemistry. In 3 main periods, phase 1 (1990-1993), phase 2 (1995-1998), and phase 3 (1999-2001), increasing sensitivity of the immunohistochemical method was provided by commercially available staining systems and shown to range from 83.6% (phase 1) to 92.0% (phase 3). The highly sensitive procedures of the antigen retrieval and peroxidase-conjugated polymer method are main contributing factors. The authors examined how these procedures influenced the distribution of positive cell population; concordance rate, including sensitivity and specificity; cutoff points; and evaluation categories. The correlation between biochemistry and immunohistochemistry was extensively studied in the 1980s and 1990s. In reference to the progress achieved in the United States and United Kingdom to control the current situation in Japan, it should be recognized that recently developed, highly sensitive procedures boost the immunoreactivity, which will affect the basic factors for technical validation.