They defined three conditions of HER2 positivity as follows (HERACLES criteria): (1) a HER2 immunohistochemical (IHC) 3 + score in ≥ 50% of CRC cells; (2) a HER2 IHC 3 + score in 10–50% of the CRC cells, and a fluorescence in situ hybridization (FISH) HER2/CEP17 ≥ 2.0 in ≥ 50% of CRC cells; (3) more than 50% of CRC cells with a HER2 IHC 2 + score and a FISH HER2/CEP17 ≥ 2.0. The gene discussed is ERBB2; the disease is colorectal carcinoma.