HER-2 (also called HER-2/neu, c-erbB2, ERBB2 or neu) is a transmembrane receptor tyrosine kinase. HER-2 is a proto-oncogene, i.e. its activation causes malignant transformation and increases the malignant potential (cell proliferation, invasiveness etc.) of the cells. Amplification of HER-2 gene invariably leads to over-expression of its protein product. The magnitude of over- expression is usually 10-100 folds or even more. Over-expressed HER-2 protein disturbs the HER-receptor family signalling networks, i.e. signalling mediated via EGFR receptor, HER-3 and HER-4. In tumours, HER-2 is over-expressed in 15-25% of primary breast cancers. Metastases usually have the same amplification status as the primary tumours. HER-2 amplification and over-expression are typical features of hormone receptor negative, rapidly growing histologic grade 2-3 tumours. Of the histologic types, Paget’s disease is almost invariably HER-2 positive, whereas only a small minority of lobular and tubular carcinomas shows HER-2 amplification. HER-2 amplification and over-expression can also be found in intestinal type gastric and gastroesophageal carcinomas, ovarian carcinomas, high grade endometrial carcinomas and some salivary duct tumours. Low-level copy number increases have been found also in rare cases of lung tumours. Because of its central importance in breast cancer therapy selection, standardization of HER-2 IHC assays and slide interpretation are of outmost clinical and economical importance.